Background: A breast-specific photoacoustic imaging (PAI) system prototype equipped with a hemispherical detector array (HDA) has been reported as a promising system configuration for providing high morphological reproducibility for vascular structures in living bodies.Methods: To image the vasculature of human limbs, a newly designed PAI system prototype (PAI-05) with an HDA with a higher density sensor arrangement was developed. The basic device configuration mimicked that of a previously reported breast-specific PAI system. A new imaging table and a holding tray for imaging a subject's limb were adopted.Results: The device’s performance was verified using a phantom. Contrast of 8.5 was obtained at a depth of 2 cm, and the viewing angle reached up to 70 degrees, showing sufficient performance for limb imaging. An arbitrary wavelength was set, and a reasonable PA signal intensity dependent on the wavelength was obtained. To prove the concept of imaging human limbs, various parts of the subject were scanned. High-quality still images of a living human with a wider size than that previously reported were obtained by scanning within the horizontal plane and averaging the images. The maximum field of view (FOV) was 270 mm × 180 mm. Even in movie mode, one-shot 3D volumetric data were obtained in an FOV range of 20 mm in diameter, which is larger than values in previous reports. By continuously acquiring these images, we were able to produce motion pictures.Conclusion: We developed a PAI prototype system equipped with an HDA suitable for imaging limbs. As a result, the subject could be scanned over a wide range while in a more comfortable position, and high-quality still images and motion pictures could be obtained. Various modalities are used in clinical practice to diagnose diseases by imaging blood vessels. These modalities have some disadvantages, such as the need for contrast medium, exposure to X-ray radiation, or expensive equipment, such as magnetic resonance imaging (MRI) systems. On the other hand, blood flow imaging is also possible with Doppler ultrasound (US), which does not require contrast medium and is not invasive; however, its spatial resolution is limited.Blood vessels are important for the delivery of oxygen and nutrients to the entire body. Vascular imaging plays an important role in the diagnosis of congenital vascular abnormalities, diseases of the blood vessels themselves, and angiogenesis associated with diseases such as cancer2. In particular, systems10 using a hemispherical detector array (HDA) as a sensor can reconstruct blood vessel images with good 3D reproducibility. We produced a prototype breast-specific PAT system 10 and used it to conduct clinical research by scanning breast cancer patients in the prone position and visualize tumor-related blood vessels caused by breast cancer. The probe arrangement of the HDA was designed to solve the "limited view problem"11 that causes PAT image degradation. This probe arrangement surrounds the measurement target with a much wider solid angle than that of a linear probe with the PAT apparatus17.Photoacoustic tomography (PAT) can be used to visualize blood vessels with high resolution noninvasivelyThe above studies demonstrated the acquisition of high-resolution 3D still images with a hemispherical probe over a large area by wide-range scanning of the measurement area.10. By analyzing the blood vessels in the palms of healthy volunteers, we showed that the tortuosity of blood vessels increases with age, suggesting the possibility of assessing the risk of diseases such as arteriosclerosis and other lifestyle diseases. In addition, by imaging perforators in the anterolateral thigh (ALT), this method was demonstrated to be effective for the preoperative planning of ALT free flaps. Although the possibility of this system being useful for imaging blood vessels in contexts other than breast cancer, especially in limbs, has been suggested, there were some related issues, such as the subject having to assume an awkward position and the measurement range being limited due to the shape of the imaging table, which was originally designed for studying breast cancer.We also scanned the healthy blood vessels in various body parts other than the breasts with these devices and reported the potential clinical usefulness of this approachWith the aim of imaging blood flow in limbs, we have developed a new PA imaging (PAI) system prototype (PAI-05) equipped with an HDA that generally follows a conventional design. Furthermore, the system is capable of real-time 3D imaging. This paper outlines the device configuration and introduces examples of biological images obtained using this device.10 equipped with an HDA that receives the PA signal. An overall image of PAI-05 is shown inx-y plane, and the x and y axes are the short and long axes of the bed unit, respectively. Thez axis is the vertical axis.The basic design of PAI-05, which was developed in cooperation with Canon, Inc., Hitachi, Ltd., and Japan Probe Co., Ltd., mimics that of the conventional prototypeWhen scanning, the body part of the subject is inserted into the holding tray on the bed unit . The pre6.x axis, 2.7 m along they axis and 0.48 m along thez axis.Conventionally, the subject's breast was inserted in the hemispherical holding cup while the subject was in the prone position. On the other hand, in the PAI-05 system, to make it easier to scan limbs, the subject lies next to the holding tray filled with water for acoustic matching. This configuration allows the subject to be scanned in a more comfortable posture than that required for imaging the palm with the previous prototype10. On the other hand, in the case of limbs, since the measurement target is often noncircular with the direction of the bone as the major axis, the scanning range is rectangular. To avoid a decrease in speed when changing the scanning direction at the vertex, the corners were scanned in a manner producing a smooth locus  was used. Using two sets of lasers, fiber bundles were used to guide laser light to the HDA, and alternate irradiation at the two wavelengths was performed. Part of the fiber bundles was pulled out to detect and synchronize the signal reception timing at the DAS unit. The diverging lens located at the base of the HDA conically spread the light to a diameter of 24.8 mm at the surface of the holding tray.One laser irradiated light at a repetition frequency of 10 Hz. Each wavelength could be selected from the wavelength range of 750 to 850 nm using an optically pumped Ti:Sa laser and a Q-switched Nd:YAG laser. The wavelength could be set at steps of 1 nm.To form a hemoglobin oxygen saturation distribution image, wavelengths of 756 and 797 nm were selected, as in the conventional case; 756 nm is the maximum point of the absorption coefficient of deoxygenated hemoglobin, and 797 nm is the isosbestic point of oxyhemoglobin and deoxygenated hemoglobin.18 was performed using two different laser systems every 50 ms. The exposure was set to be smaller than the maximum permissible exposure recommended by ANSI at any wavelength. When two lasers were set to the same wavelength, they could irradiate at 20 Hz.In PAI-05, alternate irradiation19 using a 1–3 composite piezoelectric transducer made of lead zirconate titanate (PZT) was adopted to arrange 1024 channel sensors on a 55-mm-radius hemisphere of epoxy resin. By applying this device to the hemispherical film, a piezoelectric vibrator with a three-layer structure consisting of a protective layer, a composite resonator, and a damper material was formed  installed on the bottom of the HDA, and one from the upper camera, as shown inThe PA signal was received by the HDA, and the signal data were transferred to the DAS, which was manufactured by Hitachi, Ltd. The DAS amplified the PA signal of 1024 channels at the time of light irradiation from the laser unit, simultaneously sampled 1024 channels at 60 MHz and 12 bits, and converted the signals into digital data. The digital data were sequentially transferred to the image reconstruction PC.Real-time image reconstruction could be performed during scanning, and the reconstructed PA image was displayed on the operation PC.The Digital Imaging and Communications in Medicine (DICOM) image data reconstructed inside the PAI-05 system based on the DICOM standard (version 3.0) could be automatically transferred to the DICOM image server of Kyoto University Hospital.The PAI-05 system could perform two types of imaging: one in still mode, in which a large area could be imaged by scanning with the HDA; and another in movie mode, in which a specific place was irradiated with laser light to repeatedly obtain updated PA images of that area.In still mode, images could be acquired with the scanning sizes shown inTwo types of HDA scanning operations were available in movie mode. One type was denoted as simple movie (SM) mode, in which the PA image is updated by repeatedly irradiating one spot with laser light while the HDA remained stationary on the spot. The other type was denoted as fluctuation movie (FM) mode, in which imaging was performed during continuous minute rotational motion. In any movie mode, it was possible to acquire an accumulation of images over time for a reconstructed image according to the number of times of laser light was irradiated. In FM mode, the scanning operation occurred at 3 rotation/sec such that the center of the HDA would follow the trajectory of a circle with a diameter of 3 mm .21 for PA image reconstruction. When calculating the absorption coefficient from the initial photoacoustic pressure, it is necessary to perform the light intensity correction. In this paper, however, we did not carry out it and limited the discussion within the qualitative consideration. An image was created for each shot of the laser and recorded in movie or still mode. The former method yielded real-time motion pictures, and the latter method yielded a high-quality still image by accumulating scanned images to construct an image with a wide field of view (FOV). The volume shape of the reconstructed image per irradiation, which was occurred every 50 ms, was a circular cylinder. The base was a circle with a diameter of 20 mm in thex-y plane, and the height was 30 mm in thez direction. These image reconstructions were realized in real time by pipeline-processing data transfer and reconstruction operations using five graphics processing units . The state of reconstruction during scanning was displayed on the operation PC. The voxel size when displaying the reconstruction on the display in real time was 0.1 mm in thex,y, andz directions.We used universal back-projection (UBP)11, which is commonly found in other PA systems. Adopting the HDA in the PAI-05 system remarkably alleviates the problem compared to the use of handheld (HH) devices. Nonetheless, the “limited view problem” persists in the PAI-05 system.The limitation of this system is the “limited view problem”Ideally, oxygen saturation can be calculated usingλ1 andλ2 represent wavelengths of 756 and 797 nm, respectively;r is the position to be calculated;εHb is the molar extinction coefficient of deoxyhemoglobin; andεHbΔ is the difference in the molar extinction coefficients between deoxyhemoglobin (Hb) and oxyhemoglobin (HbO2).where2) cannot be obtained due to various error factors, we refer to the parameter obtained by the two wavelengths as the S-factor15. As described previously10, the relation of the magnitude of SO2 and the S-factor is maintained within the range where the amount of irradiated light can be regarded as the same as that in a neighboring region.In real situations, since ideal hemoglobin oxygen saturation  mimicking the light absorption coefficient of blood at 797 nm was placed in Intralipos Injection 20％  diluted to 1% concentration ;aμ is the absorption coefficient, andz axis from the bottom of the tray.The phantom used in this study was as follows. Surgical thread  was used for a line spread function (LSF) evaluation (not shown). The thread was placed parallel to the horizontal plane at a depth of a few mm closer to the tray bottom from the center of curvature of the HDA.x-y plane.To evaluate the allowance of the visualization range of the “limited view problem,” we used wire phantoms  installeTo simply evaluate the wavelength dependence of the PA signal intensity, a line written on white office paper with four colors of oil-based ink pen  was used. A V-680 spectrophotometer  was used to evaluate the reflectance spectral characteristics of the office paper and oil-based ink written on the paper.For living body measurements, one healthy male subject was recruited. He was 173 cm tall, his foot was 25.5 cm long, and he was in his fifties. The hair of the imaged limb was cut beforehand with hair clippers, but when the remaining hair roots interfered with the analysis, the hair root data was excluded using the body surface detection method described above. This subject was registered as a healthy volunteer in a control group of an exploratory clinical study for examining the vascular condition of patients with a skin disease using the same PAI-05 system. In the current study, biological data from the clinical study were only utilized for the presentation of imaging examples. The results of the skin disease analyses will be reported in the near future.The present study was approved by the Ethics Committee of the Kyoto University Hospital (UMIN 000022767), and written informed consent was obtained from the subject. This study was conducted in accordance with the Declaration of Helsinki.z axis was also 0.21 mm.The performance of the system was evaluated using phantoms. The results are shown inThe image quality of the movie mode was evaluated using a wire phantom while changing the number of PA images averaged in both SM and FM modes.x: 6 mm,y: 2.5 mm,z: 2.5 mm) where the wire phantom did not exist.For the noise analysis, a plot of the background noise after normalization by the background noise without averaging was made as a function of the number of images averaged (N), as shown inIn SM mode, reducing the background noise only slightly reduced the system noise with respect to N. The FM mode showed a greater noise reduction effect than the SM mode. To analyze the noise reduction effect in FM mode,With the PAI-05 system, the wavelength could be arbitrarily selected from 750 to 850 nm.Next, the living subject was imaged. This system was newly designed to facilitate the imaging of limbs. We designed the holding tray to be shallower and wider than before to make it more comfortable for a subject to assume the posture required for scanning.8.Similar to the results of the phantom experiments, as shown inIn the image of the sole of the foot shown inThe thigh shown in15 using alternating irradiation from two different lasers10. A PA image showing blood vessels that could be distinguished as an artery or vein was obtained.In the PAI-05 system, two laser wavelengths can be arbitrarily selected within the range of 750 to 850 nm. Stable S-factor images were obtained by adopting alternating irradiation.4. Our system could provide more extensive motion pictures.Zip file containing the underlying data of the presented results in excel filesClick here for additional data file.Copyright: © 2019 Nagae K et al.2019Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).In the PAI-05 system, the HDA consisted of 1024 high-density sensors arranged inside a hemispherical casing with a diameter of 110 mm.10, approximately 500 discrete rod-shaped sensors were inserted into a hemispherical casing with a diameter of 254 mm, but designing such a high-density arrangement for this study might have been difficult with conventional methods. The HDA design developed for this study using film-type sensors has the potential to greatly simplify the sensor manufacturing process for practical use because it was able to realize a 1024-channel arrangement, which may be difficult with discrete elements. This design made it possible to obtain images with less noise even with one shot, contributing to the realization of real-time motion pictures.In the previous designs17, the reproducibility of the blood vessel morphology in the PA images seems to be poor. Although the resolution seems to be good in the plane of a previously reported ring sensor24, the resolution in the direction normal to the ring surface is reportedly several mm or more. 3D structural analysis using images with such large anisotropy would be difficult.While real-time motion pictures in PAT have mainly been reported in combination with conventional B-mode ultrasound10, PA images obtained by a PAI system with an HDA show nearly isotropic spatial resolution, which is considered optimal for reproducing the morphology of blood vessels. Information for diagnosis can be obtained by performing 3D observations from different directions using not only still image but also real-time motion pictures. There is no doubt that larger imaging areas for capturing both still images and motion pictures will greatly contribute to the diagnosis of conditions in living organisms.As shown in7. Clinical research in biological organisms should be continued, and diagnostic capability of the system should be verified.Regarding the phantom evaluation, sufficient contrast was obtained at a depth of 2 cm in still mode. This depth is nearly sufficient for imaging the subcutaneous vessels of limbs. Linear-type phantoms could be imaged from 0 to 70 degrees with respect to the evaluation of the “limited view problem,” so it can be expected that most actual blood vessels in the living subject can be observed using the PAI-05 system. On the other hand, there is still an issue that perforators rising from deep regions may be difficult to visualize, as noted in a previous paperIn the phantom experiment for evaluating the image quality in movie mode, the noise could be reduced by increasing the number of images averaged (N), as shown inAs for the evaluation of the living subject, it was possible to appropriately scan the limbs by designing the system configuration to be suitable for limb imaging. Since it is now possible to obtain PA images in a wide range, it is expected that diagnosing conditions affecting blood vessel will be made easier by viewing more complete images. These images will also be able to provide clinically useful information, such as that necessary for preoperative planning.10 could not only reduce the dead space when scanning long body parts but also shorten the scanning time.Adopting a rectangular spiral scan instead of the conventional circular spiralNonetheless, because the scanning time varies depending on the size of the area when applied for routine clinical diagnosis, physicians may need to carefully determine the minimum required scanning range in consideration of the state of the patient.The PAI-05 system is limited to four scanning modes, as shown in15, may have to be considered.There were body parts that could not be imaged as they were protruding from the water in the holding tray. This may be a large problem to be solved, especially in the context of scanning elderly patients or areas that require an awkward posture. Another approach for acoustic matching between the subject and the holding tray, such as applying an acoustic matching gel226. This capability could also enable the imaging of externally added dyes, such as indocyanine green (ICG), and thus enhance the applicability of PAT27. There are still no useful clinical application based on the clinical evidence of real-time 3D PAI, but new clinical applications of our PAI system will be developed and are expected to be proven in the near future. For example, diagnostic imaging using molecular probes is currently under development for future applications. Additionally, high-definition 3D imaging modes could potentially clarify drug delivery characteristics with high temporal resolution. The potential applications of the PAI-05 system reported here could be considered great advances in PAT technology. Clinical research in patients will be conducted in the future. The device performance for actual human subjects will be evaluated at that time.The ability to arbitrarily select the wavelength may contribute to improving the quantitative analysis of SO10.Clinical research in patients will be conducted in the future. A high-quality 3D motion picture  with submillimeter resolution may be difficult even with CT or MRI, and it is expected that new clinical findings will be obtained with the PAI-05 system. This system is promising for obtaining a wide range of high-definition images not only for the preoperative planning of free flap surgery but also for the PAT-based diagnosis of breast cancer, as previously reportedIn summary, we developed a new system, named PAI-05, dedicated to limb imaging and showed its properties in phantom experiments. We also imaged the limbs of a living subject in a wide range using the PAI-05 system. As with the conventional prototype, a high-resolution arteriovenous image was obtained by label-free imaging. Real-time motion pictures in an area with a diameter of 20 mm could be obtained. We expect to develop new clinical applications for the new PAT system.The data referenced by this article are under copyright with the following copyright statement: Copyright: © 2019 Nagae K et al.Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).https://doi.org/10.5256/f1000research.16743.d22486928F1000Research: Dataset 1. Zip file containing the underlying data of the presented results in excel files,Description of content No further comments.I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. This paper describes a state-of-the-art system, which is capable of real-time photoacoustic imaging of a living human body. The authors evaluated fundamental characteristics of the system, such as spatial resolution and angle-dependent visibility of a target, and also showed the feasibility of the system in in vivo imaging of vascular trees in a living human body. The system is able to visualize small vessels with good resolution and contrast. The contents of the paper would be of interest for the readers. Upon indexing, I suggest revisions described below:There are number of referenced papers published from authors' group. On the other hand, the papers from other research groups seem few. Are there no more related works from other research groups?Although the method for image reconstruction is described in [21], it would be better to describe how to do that briefly. Particularly, the diverged laser light has a significant spatial inhomogeneity as shown in Fig. 3. Can you obtain an image by one shot of laser pulse with such a spatial inhomogeneity? Using such a diverging light source, photoacoustic signals would also be spatially inhomogeneous. Do you need any correction compensating for such a spatial inhomogeneity in the light intensity?It would be more informative if you describe the reason for the use of fluctuation of the light source in the fluctuation mode (FM). Does the fluctuation change the spatial distribution of artifacts? If so, it is understandable that image quality is improved by averaging.The size of an ultrasonic transducer element is relatively large (2 mm). I understand that the sensitivity of each transducer element should be high, but are there any effect of the element directivity on image quality, such as artifact generation?In p. 7 and l. 2 in the right column, epsilon_Delta Hb should be epsilon_Hb?In p. 7 and l. 3 in the right column, I found an expression "epsilon_Delta Hb and is". "and" should be removed?As explained in the paper, the scan time increases with widening the field of view. Do you need any motion compensation technique because the spatial resolution is very high?In the case of alternative laser irradiation, are there any effects of movements of blood cells during the repetition period of 50 ms? In the in vivo experimental results, relatively large vessels are also visualized, and movements of blood cells in such a relatively large vessel would be significant owing to relatively high flow velocity.In Fig. 6b, I can see some artifacts. Such a distribution of the artifacts (sidelobes?) depends on the spatial arrangement of array elements based on the Fibonacci grid? It would be better to describe why artifacts can be suppressed by the Fibonacci grid and how large the sidelobe level is when a regular grid is used.Particularly in Fig. 6e, I can see remarkable range (y-direction) sidelobes. What is the source of those sidelobes? Also, such sidelobe components do not affect the estimation of oxygen saturation?  I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Dear Prof. Hideyuki Hasegawa (Reviewer #2)The authors would like to thank Reviewer #2 for your decision of “Approved". In order to aim more high-quality paper, we responded to the comments of Reviewer # 2 and made corrections as necessary(1)    Response: Not revisedAs well-known, there are many papers on PAT, but there are not many papers as for PAT with HDA, especially for actual clinical use. Although there are various system configurations such as linear probe method, method using Fabry Perot, ring-shaped method and so on, there are too many to describe all other methods in a well-balanced manner. For this reason, we focused on HDA-PAT system and its clinical use. Based on this policy, we did not add the other references.(2)    Response: AgreedYour point is right. When calculating the absorption coefficient from the initial sound pressure, it is necessary to correct the spatial non-uniformity of the light intensity including the in-vivo depth direction.On the other hand, if only image evaluation is performed qualitatively, it is not always necessary to correct the light intensity. This is because, in the Still mode, spatial nonuniformity of light intensity is corrected by averaging images obtained by scanning the hemispherical sensor in a wide range.In the Movie mode, since the light nonuniformity cannot be compensated, the signal may become dark around the image. But we can evaluate the image qualitatively. We revised the following sentences.(Before)We used universal back-projection (UBP) [21] for PA image reconstruction.(After)We used universal back-projection (UBP) [21] for PA image reconstruction. When calculating the absorption coefficient from the initial photoacoustic pressure, it is necessary to perform the light intensity correction. In this paper, however, we did not carry out it and limited the discussion within the qualitative consideration.(3)    Response: Agreed Your point is right. We revised the following sentences.(After)The spatial distribution of artifacts is changed by shifting the relative position of the HDA with respect to the absorber. Artifacts in FM can be suppressed by averaging the various spatial distributions.(4)    Response: Not revisedWe are reconstructing a spatial region with high receiving sensitivity of photoacoustic waves specified by element size and element placement. Since the image reconstruction range is limited, we have confirmed the influence of artifacts is not large.On the other hand, if the element size is smaller, image reconstruction in a wider spatial region becomes possible. However, it is necessary to expand the light irradiation region. In that case, there is a possibility that the artifact increases due to increase of artifact sources. We made no additional sentence.(5)    Response: Agreed Your point is right. We revised the following sentences.(Before)ε∆Hb is the molar extinction coefficient of deoxyhemoglobin;(After)εHb is the molar extinction coefficient of deoxyhemoglobin;(6) Response: Agreed Your point is right. We commented on the docx file.(7)    Response: Agreed but no revisedYes. We consider that the motion compensation technique can derive a better image, but it is not utilized in this paper.We can do it as written in the previous article, so we will adopt it as necessary in future clinical research. We made no additional sentence.(8)    Response: Not revised With the spatial resolution of the current device, we cannot discriminate red blood cells individually, so we believe there is no effect of blood flow. We made no additional sentence.(9)    Response: Not revisedThe artifacts seen in Fig. 6 are generated not by arrangement of the elements but by the discontinuation of the detectors around edges of the HDA.The effectiveness of adopting Fibonacci grid is to suppress the artifacts generated in a specific direction since the detectable area of each element is uniform. We made no additional sentence and quantitative arguments.(10)    Response: Not revised It is also an artifact due to the discontinuation of the detectors around edges of the HDA as same as the (9). Oxygen saturation of blood vessels overlaid on this artifact may be affected by artifacts. We made no additional sentence.Best regards,Kenichi Nagae and Yasufumi Asao This manuscript demonstrates performance of the latest photoacoustic system from Canon Inc. The images are very impressive and definitely showcase the potential of photoacoustic imaging for clinical applications. Compared to the previous generation, major improvements in the current system include the use of a 1024-element transducer array (vs. 512 elements), implementation of dual wavelength imaging, a flat bed for limb imaging, and dynamic imaging of motion. Overall the manuscript is well written and the study is comprehensive.Please quantify the imaging depth in human. Calculation in phantom is not sufficient as the phantom composition could not precisely represent the optical attenuation of human tissue.1. Could the system be miniaturized for that application? Foot imaging could be used for chronic ulcer assessment. However, most of those patients are immobile and the imaging pose may not be ideal for these patients.Application of the system is unclear and needs to be clarified. The palm images could be used for biometric application as mentioned in a previous publicationThe authors suggested ICG imaging. For that application, photoacoustic imaging will compete with fluorescence imaging, such as the SPY system from Novadaq. What would be the pros and cons of PAI in comparison to a clinical fluorescence imaging system?Please indicate the magnitude of amplification in the data acquisition system. 2. The system has been improved over years to 1024 elements. Is there a cut-off number, beyond which further increase in element number will not improve the image quality? The original system from Dr. Kruger's group used a 128-element hemispherical arrayAfter reconstruction, did the authors use any image processing techniques to enhance vascular structures? The study could be further improved in the following aspects:I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Dear Prof. Jun Xia (Reviewer #1)The authors would like to thank Reviewer #1 for your detail comments and suggestions. It is a great honor to receive high evaluation. However, if there is concern about duplication with the results and discussion of clinical research papers planned to be submitted in the future, we cannot describe that point deeply. Therefore, there may be points that are not answered enough for comments.(1)    Response: Partially agreedWe agree that the phantom's evaluation is inadequate as you pointed out, and evaluation by the human being is indispensable for showing the device performance. Nonetheless, we think that it is not good data to quantify it with just one healthy person this paper. There is no guarantee that this person is typical.The results of clinical research using the device disclosed this time will be papers in future. The depth performance of human imaging should be discussed in multiple cases among them. So, we added the following sentence to the discussion section.Clinical research in patients will be conducted in the future. The device performance for actual human subjects will be evaluated at that time.(2)    Response: Agreed but not revisedThe applicability to biometric authentication has already been mentioned in reference [6], so it is omitted in this paper.In this paper, we designed the device that can measure limbs in a versatile medical usage. It is primarily targeted for medical applications and has been evaluated as useful for research on plastic surgery area using this device. Through clinical research, issues for patients have come to be seen and we are aware that the current situation is not ideal as you pointed out. Therefore, it is described as follows.“This may be a large problem to be solved, especially in the context of scanning elderly patients or areas that require an awkward posture. Another approach for acoustic matching between the subject and the holding tray, such as applying an acoustic matching gel [15], may have to be considered.”It is no doubt that it can be downsized by technical development, but we have not confirmed details, so I think that it is not appropriate to describe as a paper.Further clinical issues to be solved should be listed in individual clinical papers to be submitted in the future.We would like to maintain the text from the original paper without any additional sentence.(3)    Response: Agreed but not revisedWe also started clinical studies using ICG imaging, and also presented the results of comparison between SPY (or PDE) and PAI at domestic and international conferences. It will be appeared in a clinical paper shortly. Since conflicts are concerned, we would like to avoid detailed description. (4)    Response: AgreedWe added the sentence to the device configuration section.We set the amplification rate to 48 dB in this study.(5)    Response: Agreed but not revisedWe calculated it and we concluded that until the densest sensor arrangement on the hemispherical array, the image quality, which corresponds the number of artifacts, monotonically improves in proportion to the number of sensors. In other words, there is no cutoff number.We did not modify the text for this comment.(6)    Response: Not revisedNo special image processing has been done. We made no additional sentence.Best regards,Kenichi Nagae and Yasufumi Asao


We present a method of segmenting human parts in depth images, when provided the image positions of the body parts. The goal is to facilitate per-pixel labelling of large datasets of human images, which are used for training and testing algorithms for pose estimation and automatic segmentation. A common technique in image segmentation is to represent an image as a two-dimensional grid graph, with one node for each pixel and edges between neighbouring pixels. We introduce a graph with distinct layers of nodes to model occlusion of the body by the arms. Once the graph is constructed, the annotated part positions are used as seeds for a standard interactive segmentation algorithm. Our method is evaluated on two public datasets containing depth images of humans from a frontal view. It produces a mean per-class accuracy of 93.55% on the first dataset, compared to 87.91% (random forest and graph cuts) and 90.31% (random forest and Markov random field). It also achieves a per-class accuracy of 90.60% on the second dataset. Future work can experiment with various methods for creating the graph layers to accurately model occlusion. Segmenting the parts or limbs of a human body has applications for pose estimation , roboticIn this problem, we are provided a depth image, a foreground segmentation of the human figure and a set of image positions for the body parts. The objective is to assign each pixel in the foreground to a body part. Our approach is to use the part positions in conjunction with an interactive image segmentation algorithm.n-dimensional image, which is classified into k distinct regions. A user specifies seed pixels (or voxels) in regions of interest that are given a label from one to k. The regions are segmented using the values of the pixels. In this application, k is the number of body parts, and the pixels have only depth values.Interactive image segmentation involves an While interactive segmentation algorithms can segment an image into logical regions, it can be difficult to apply them to human part segmentation, due to the presence of self-occlusion: when some regions of the body are occluded by others. In response, we use a graph representation that is designed to handle occlusion. The assumption is made that the arms are the only regions that can potentially occlude other parts. We create a grid graph with one to three layers: representing the base body, the right arm and the left arm. In this formulation, a single pixel in the image can be represented by more than one node in the graph. A standard interactive segmentation algorithm can then be applied to this layered graph, resulting in a more accurate segmentation of human limbs.The paper is organized as follows. Relevant literature commonly refers to segmenting regions of the body as human limb segmentation. We refer to our system as human part segmentation, to make the distinction between limbs  and parts .Segmenting human limbs has been applied to single RGB images ,7, RGB vHuman limb segmentation from RGB-D data has seen recent application to mobility assistance robots . Using RThe authors in  introducThe work of  involvedThe algorithms of ,4,10 allThe following algorithms were developed for general interactive image segmentation. They all share the properties of operating on a grid structure, such as a graph or lattice. The segmentation results depend on user-defined seeds and labels and the difference in value between pixels in the same local neighbourhood.The original graph cuts algorithm  was inteu and v, i.e., a random walker is more likely to cross an edge between similar pixels. Each seed pixel is given a label from one to k.The random walker (RW) algorithm  was desii, the seed pixels labelled i are given a unit potential while the other seeds are set to zero. The resulting potential at each unlabelled pixel u is the probability that a random walker beginning on u will first reach a seed pixel with label i. Once all k probabilities have been calculated, the pixel is assigned the label with the highest probability.The algorithm makes use of an equivalence theorem between random walks on a graph and electric potentials in a grid circuit. Each edge in the graph is represented by a resistance that is the inverse of the edge weight. For each label By representing the problem as an electric circuit, the image is segmented by solving a series of linear equations, rather than actually simulating a random walk.S, a local neighbourhood N that defines adjacent pixels and a transition function k in the image. At each time step, a transition function is applied to pixels in the local neighbourhood of the seeds, which allows non-seed pixels to be labelled. The authors make the analogy of k competing bacteria cultures, which grow from their seed positions and attempt to claim new pixels as territory. The transition function is designed so that the competing populations eventually reach a stable configuration, segmenting the full image.Like the RW algorithm, GrowCut  is desigOur review of related works has shown the need for assisted segmentation of human depth datasets, and a means of achieving this via interactive segmentation. GrowCut and RW were both initially considered for this application. RW was eventually chosen for its speed of computation and tendency to produce smooth boundaries between regions. As described in the following section, it is used twice: once for segmenting the arms to create the layered graph and finally to produce the output segmentation.i, column j is connected to its four-neighbourhood in the image: the pixels at u. This is the standard weighting function for RW [u. The parameter The depth image is converted into an undirected grid graph, with one node for each pixel in the foreground. The pixel at row n for RW . In thisested in .We first aim to segment the two arm regions, as we assume these are the regions that are potentially occluding other parts of the body.As described in w, as shown in P for hand X is used to segment arm X (left or right).To increase the variance in probability values, an extra ‘dummy’ node is added to the graph. This node is connected to every node in the grid graph by an edge with a small weight P found in If the arm is occluding the body, there will be a significant difference in depth between pixels on the arm and neighbouring pixels on the body. This will also be evident in the probability matrix P are clustered using the mean shift algorithm [n uniformly-spaced values are taken from the sorted list and clustered with mean shift, resulting in k clusters. The value of n can be tuned by the user for their specific dataset. Mean shift automatically determines the number of clusters.The probability values of lgorithm  with a GA new image i, the full arm segment is the union of segments in i.An iterative process is used to find the arm segment that minimizes a cost function, as explained below. Beginning with the segment on P . An example is shown in The image gradient captures information about the local change in pixel values . It retuThe binary arm segment A new binary image The cost of iB to cut across a strong gradient line, while a iB that is too large will cut across a strong gradient line itself. This is evident in In essence, an arm segment Algorithm 1 shows the pseudocode for the iterative process that segments the arm. It selects the arm segment that minimizes the cost defined in Equation . After tAlgorithm 1 Arm segmentation.1:PSort values of probability matrix 2:n evenly-spaced samples from sorted listSelect 3:4:P5:function ArmCost are assumed to be the only parts that can occlude the body; therefore, they are the only candidates for belonging to layer X. If the segmentation for arm X is valid, the hand of this arm must belong to layer X in the graph. The elbow is assigned to layer X only if its position is inside the arm segment Every annotated part position must be assigned to its correct layer in the graph In order to run an interactive segmentation algorithm on the graph, a subset of nodes must be specified as seeds. The provided body part positions are used as seed nodes, with labels one to A and B. This line A and B, respectively. The user specifies a value r, which is the ratio of the length of More seed nodes can be added by drawing lines between adjacent body parts. Bresenham’s algorithm  is used i is assigned to the layer of part i. Thus, seed pixels on the image are converted to seed nodes in the layered graph.Each pixel in G. The RW algorithm is used for the final segmentation. Every node in the graph is given a label by the algorithm. The final output image has the same size as the original depth image, and each pixel in the foreground receives a label. Pixels in arm segment X are represented by a node in Once the seed nodes and labels have been determined, an interactive image segmentation algorithm can be run on the layered graph Our method is tested on two public datasets of human depth images with segmented parts: “Human Limbs from RGBD data”  and “HumDataset 1 includes two actors in three video sessions, performing gestures in front of a Kinect v1 camera. Only the upper body is shown. The accompanying ground truth images have seven labels: torso, right/left upper arm, right/left lower arm and right/left hand. Each frame is a Our method is tested on one case from Dataset 2: sitting poses viewed from the front. This set contains nearly 5000 depth images of the full human body. Each frame is a The RW algorithm is performed using an open source MATLAB program written by the author of the algorithm . In thisi, the annotated part position is the foreground pixel closest to the centroid of all pixels labelled i (the pixel is not required to have truth label i itself).Each input body part position is annotated using the ground truth labels of the test dataset. For each part To show that our method offers an improvement over generic interactive image segmentation, the standard RW algorithm is run on all frames with the annotated part positions as seed pixels, using the same Some additional pre-processing is used for this dataset. As an exception to the annotation rule defined above, the torso pixel is the mean position of the left and right upper arm pixels, whenever both of these arm parts exist. Some of the depth images include abnormally high depth values along the outline of the human figure, interfering with the RW algorithm. Therefore, the depth images are pre-processed to remove pixels with values greater than 2.5 metres. The same pixels are removed from the truth images.r is set to Two versions of our method are tested. The first  uses only the seven part positions as seeds for the segmentation. The second  adds a line of seed pixels between the torso and the two upper arm positions, as per The results of our method are also compared to the best performance of two algorithms tested on the same dataset ,10.Because of the relative positions of the ground truth labels for this dataset, it was decided that adding a line of seed pixels was unnecessary. Thus, only the simple version of our method is tested on this dataset, using the 11 annotated part positions as seed pixels.i and predicted label j. The matrix has dimensions L is the number of labels.Two metrics are used to evaluate our method: the per-class accuracy ribed in . The coni is the number of pixels correctly labelled i over the total number of pixels labelled i. This metric has been previously used to report results on Dataset 1 [The per-class accuracy for label ataset 1 ,10.(11)i is the number of pixels labelled i in both images over the number of pixels labelled i in either image, i.e., the intersection over union. This has been the standard evaluation metric for the PASCAL challenge since 2008 [The Jaccard index for label nce 2008 .(12)JIiA and B, respectively. A win for method A is recorded when To evaluate one method against another, the mean Qualitative results are shown in The mean per-class accuracy is shown in A over method B. For both metrics, the two versions of our method outperform the standard RW algorithm. Examining the total differentials, adding line seeds causes a slight decrease in per-class accuracy (Qualitative results for Dataset 2 are shown in As seen in the first and fourth row of The first two rows of Connecting graph layers  allows ti to the total number of pixels labelled i, an overly large arm segment will still have a high accuracy. If the torso pixels are misclassified as upper arm, the per-class accuracy does not greatly reduce because the torso is so large by comparison. For this reason, we consider the Jaccard index to be a more discriminative metric and conclude that adding a line of seed pixels is overall advantageous to our method.Between the two versions of our method tested on Dataset 1, there is a trade-off between the two evaluation metrics. We hypothesize that adding line seed pixels greatly increases the Jaccard index because it limits the size of the upper arm segments. The left and right upper arm values increase from re added . Since tThe results indicate that our method offers superior performance to the standard RW algorithm. By creating a layered graph structure, there is an increase in both the Jaccard index and the per-class accuracy. Our method also outperforms two state of the art algorithms ,10 on thWe have presented a graph-based approach to segmenting human parts from depth images, given the image positions of each part. We propose a layered graph structure that can handle self-occlusion by the arms. The provided part positions are used to determine seed nodes and labels for a standard interactive segmentation algorithm. This work is intended to facilitate the labelling of human segmentation datasets, which can be used for training and testing new algorithms.Future work in this area could aim to optimize the two https://github.com/ajhynes7.The main conclusion from this study is that a layered graph representation of an image can improve the performance of an interactive segmentation algorithm, when segmenting body parts with a small number of seed pixels. This has been demonstrated on two depth datasets of humans from a frontal perspective. To encourage further research on this topic, our implementation will be made publicly available at


This paper explores the effects that variation in the coalescence efficiency of the Venus cloud particles can have on the structure of the Venus cloud. It is motivated by the acknowledgment of uncertainties in the measured parameters—and the assumptions made to account for them—that define our present knowledge of the particle characteristics. Specifically, we explore the consequence of allowing the coalescence efficiency of supercooled sulfuric acid in the upper clouds to tend to zero. This produces a cloud that occasionally exhibits an enhancement of small particles at altitude (similar to the upper hazes observed by Pioneer Venus and subsequently shown to be somewhat transient). This simulated cloud occasionally exhibits a rapid growth of particle size near cloud base, exhibiting characteristics similar to those seen in the controversial Mode 3 particles. These results demonstrate that a subset of the variations observed as near-infrared opacity variations in the lower and middle clouds of Venus can be explained by microphysical, in addition to dynamical, variations. Furthermore, the existence of a population of particles exhibiting less efficient coalescence efficiencies would support the likelihood of conditions suitable for charge exchange, hence lightning, in the Venus clouds. We recommend future laboratory studies on the coalescence properties of sulfuric acid under the range of conditions experienced in the Venus clouds. We also recommend future in situ measurements to better characterize the properties of the cloud particles themselves, especially composition and particle habits (shapes). The clouds are a defining characteristic of the atmosphere of Venus. They completely enshroud the planet between the altitudes of about 50 and 70 km. They are composed primarily of sulfuric acid Sill , but othThe most comprehensive description of the Venus cloud particle sizes comes from the Pioneer Venus mission, with subsequent measurements by the VeGa decent probes largely confirming the Pioneer Venus results. In situ observations of the condensational clouds by Pioneer Venus LCPS suggest that two size modes of particles are seen above 57 km, while three modes are seen between 48 and 57 km (Knollenberg and Hunten The Pioneer Venus Orbiter Cloud PhotoPolarimeter (OCPP)  sampled the clouds of Venus from an altitude of about 65 km down to the surface .The LCPS descended at In addition to the Mode 3 controversy, the smallest mode of particles measured by the LCPS is similarly unconstrained. Note from Figure 10 of Knollenberg and Hunten  that thei.e., in the upper clouds and hazes). If frozen or glass-like particles were to exist at these altitudes, their coalescence properties would differ from those of liquid sulfuric acid, and hence, the expected size distributions of the cloud particles may vary. Furthermore, as suggested by McGouldrick et al. , then our models lose a little fidelity, especially when we consider a range of latitudinal profiles. The main focus of this work, however, is an exploration of the consequences of the various processes at work in the Venus clouds, so the comparison to the nominal case is more relevant than a comparison to observation, in many cases.The atmospheric profiles defined by the Venus International Reference Atmosphere (VIRA)  or via binary homogeneous nucleation of water and sulfuric acid molecules.In our previous work, we assumed that a known population of particles observed by LCPS and other descent probes could serve as CCN for activating sulfuric acid cloud droplets. These small particles were observed at altitudes well below that which sulfuric acid may stably exist in the liquid phase, so it can be safely assumed that they are not sulfuric acid, but can perhaps serve as activation sites for sulfuric acid. For our simulations that extend above 60 km, however, there is no solid evidence for the existence of involatile particles. Theoretical chemical studies suggest that a population of sulfur allotropes should exist (Yung and DeMore T), and relative humidity of water vapor . Because extremely high supersaturations are required to reach this state, once a germ is formed, it has the potential to rapidly increase in size via diffusional growth. Because the processes that drive nucleation are so rapid, it is necessary to parameterize the activation process in a microphysical model. Here, we use the parameterization by Vehkamäki et al. . This pamentclass2pt{minimIn order to be able to distinguish between the effects of these changes on the condensational cloud versus the coupled photochemical and condensational clouds, we first perform a series of simulations on a model with a domain from 40 to 60 km, in which the photochemical upper cloud is treated as a boundary condition of particles at the top of the model domain.This simulation is performed in order to verify that the updates made to the model since its last published use have not significantly altered the characteristics of the simulated cloud. The intention is to demonstrate the consistency between the new and the old simulations, hence to lend additional credence to the current results. We perform these simulations for the five latitude regions specified in the VIRA model. As a shorthand, we call the 0°–30° profile, ‘equatorial,’ the 30°–45° and 45°−60° profiles ‘mid-latitude’ , and the 60°–75° and 75°–90° profiles ‘polar’ . The equatorial profile in these simulations is the one most fairly compared to the previous simulations by McGouldrick and Toon .In Fig. It is important to note that the LCPS profile merely represents a single profile (at 3°S) of particle size characteristics from a single instrument falling through the Venus atmosphere. Though these nearly 40-year-old measurements represent the highest resolution in situ measurements of the Venus clouds even today, we should not afford too much meaning to them. Nephelometers, remote sensing, and the slightly lower-resolution particle size spectrometers on the VeGa landers all indicate that the size distribution and number concentration of the aerosol in the Venus clouds are both highly variable in space and time. These measurements also show that the ‘middle’ cloud deck between about 50 and 57 km is a bit more stable over time, when compared with the much more flighty ‘lower’ cloud deck. Hence by comparing our simulations with these data, we are comparing the best available ground truth at our disposal. We furthermore are more concerned with the order of magnitude agreement than the details; consistency between simulation and observation in the 50–57 km region is taken to be more of an indicator of success than the highly variable 48–50 km region, and the somewhat undersampled region above 60 km.The mid-latitude and equatorial profiles closely match the mass loading of the LCPS observations throughout the condensational cloud. However, each of these lacks the sharp increase in cloud mass loading observed in the LCPS observations as the ‘lower cloud’ between the altitudes of about 48 and 50 km. This morphology of the vertical profile represented by the observed lower cloud, however, is closely matched by the two polar profiles, if not quite in magnitude, falling a factor of two short, although this sharp increase in mass loading occurs at much lower altitudes (~ 45 km) than observed by LCPS (~ 49 km), due to the deeper location of the cloud base at those polar latitudes. Since the 40 km boundary condition on sulfuric acid is identical across all latitudes simulated here, the lower cloud base at the polar latitudes is due entirely to the cooler temperature profile within the 40–60 km region of the Venus atmosphere.i.e., area-weighted average—radius of the aerosols in our simulations to that derived from LCPS data. In each case, there is some agreement with the LCPS profiles. Typical effective radii through the simulated middle cloud (between about 50 and 57 km) are between about 2.5–3.0 μm among the five simulations, while the radii calculated from the distributions used to fit the LCPS measurements were just under 4.0 μm. Each profile demonstrates an increase in effective radius with proximity to the cloud base. This is partly the result of evaporation of cloud particles, which tends to remove the smallest particles entirely, while reducing only slightly the typical sizes of the larger particles. It is also the result of a steady growth of cloud aerosol that results from the increasing vapor pressure  with depth.Also in Fig. In Fig. However, despite being consistent with the accepted variations in the vertical structure of the atmosphere, the deeper cloud base found in these simulations is consistent with neither remote sensing retrievals of cloud base  in the aerosol, then water is liberated. The water vapor mixing ratio indicates the transport of water from the cloud droplets introduced at the upper model boundary into the cloud domain. The equilibrium weight percent of acid decreases from about 80% near the top of the model domain to over 90% near the cloud base. Thus, as droplets fall through the cloud, they tend to lose water in order to maintain equilibrium with their surroundings. Note that this implies an upward diffusion of water vapor from cloud base to cloud top. However, because the deposition region for the water vapor lies lower in altitude than the prescribed increase in eddy diffusion coefficient, this water is slow to be redistributed back to the cloud top and plays a role in the differences between the simulated cloud among the various latitude profiles.In Fig. None of our latitudinal profiles demonstrate a significant gap in the clouds, as indicated by the LCPS observations at about 57 km. However, we note that in McGouldrick and Toon , this mii.e., 1.0 μm) mode of sulfuric acid droplets is not seen, with the exception of the model layers closest to the top boundary condition. Finally, the CCN involatile mode appears to do a good job of matching the observational data, except that the largest particles of Mode 1 appear to have been activated and have since grown into larger cloud particles. Some of these seeming discrepancies may be related. For instance, I have not calculated the deliquesced radius of the CCN in subsaturated conditions. If the CCN are soluble in sulfuric acid, then even at supersaturations less than the critical supersaturation, they will attract vapor molecules and swell to radii slightly larger than that of the dry CCN. While it is unlikely that this could explain the ‘missing’ Mode 2 of droplets, it would explain why the modeled CCN are actually so small (r < 0.3 μm) that they would not be detectable by LCPS. Note also that the typical size of the sulfuric acid droplets becomes recognizably larger than the observations only a few kilometers below the boundary condition. This may suggest either an inhibition to particle growth that we are not yet considering, or the existence of multiple sinks for the sulfuric acid. Alternately, the additional mode of particles could be a more transient phenomenon. Later in this paper, we explore these possibilities.In Fig. In Fig. Next, I describe the results of a set of simulations in which coagulation is strictly forbidden. This coagulation-inhibited case is not meant to represent an expected behavior in the clouds, but rather to represent an extreme end member for quantifying the effects of the efficiency of coalescence on the distribution and composition of the Venus clouds.2 (2.5%) for the equatorial profile, to an increase of 3.62 g/m2 (4.8%) for the most polar profile. Note that this simulation does not permit the CCN to self-coagulate; they may only be scavenged by the droplets. And, since the number concentrations are small, Brownian coagulation is likely to be a non-factor. Gravitational collection and coalescence is a possibility, but since in our simulations the 1 μm  mode grows condensationally to become the larger mode, and the smaller mode consists of tiny CCN, this mechanism is not expected to add much mass to the condensational cloud.Returning to Table Figure Here I describe the results of a set of simulations in which the acid vapor boundary condition is reduced by a factor of two. The reason for testing this is that the true value of the acid vapor boundary condition below the cloud base has proven rather difficult to constrain. The value of the sulfuric acid vapor mixing ratio has been most extensively measured by means of radio occultations, taking advantage of the fact that sulfuric acid absorbs radio emission at frequencies within the S-band and X-band , is not something to be expected, unless we have created a situation where two wrongs make a right.The contour plots of the mass loading and effective radius with time in this simulation Fig.  demonstrIn Table Many of the simulations did not achieve a true steady state. Rather, they tended to oscillate between two end-member quasi-steady-state profiles. Because of this, it is necessary to express the column abundance in terms of a mean and variation in Table As mentioned above, the condensational cloud in this simulation  contains smaller mass loadings that are more consistent with the 40–60 km simulations that suppressed the upper cloud boundary condition. Furthermore, as might be expected, the changes in the photochemical production rates had a larger effect on the column abundance of the photochemical cloud than on the condensational clouds. This is likely a robust result, assuming that the timescales for the thermochemical destruction of sulfuric acid, and subsequent depletion of the reservoir, are likely to occur at somewhat longer timescales than the microphysical processes observed here (Krasnopolsky 6 molecules/cm3 at 70 km).In Fig. i et al.  above thi et al. , who fouIn Fig. insoluble involatile particles. Thus, either the Mode 1 particles are not soluble in sulfuric acid and cannot be considered to reduce the vapor pressure via the solute effect in the condensation of sulfuric acid in the condensational clouds, or the processes of aerosol activation and scavenging by coagulation must remove all of the Mode 1 involatile particles before they can reach the photochemical cloud. In this scenario, the Mode 1 particles are then understood to be a population of sulfur allotropes or other species that is immiscible in sulfuric acid. These particles will be ubiquitous throughout the clouds, and below. The Mode 2 particles are the products of photochemical production of sulfuric acid, binary homogeneous nucleation and subsequent condensational and coalescent growth. Any particles that could be considered Mode 3 would then simply be the large size wing of the size distribution in these simulations.In the ‘equ’ and ‘mid1’ profiles, we do not see obvious evidence for the generation of numerous small droplets. This is possibly because sufficient CCN have reached to this altitude in these simulations, permitting activation of sulfuric acid aerosols, hence short-circuiting the binary homogeneous nucleation step. This suggests that the presence of suitable CCN can have a significant effect on the structure of the upper part of the Venus clouds, including the photochemical cloud. Note that previous work by James et al.  suggesteHere we present the results of simulations that, similar to Gao et al. , utilizeThe plot of the mixing ratios from this simulation Fig.  indicateConsistent with the results of the simulations in which the mass loading and effective radius were found to increase in response to an increase in photochemical production rates, this simulation in which the photochemical production rate was decreased results in decreases of photochemical cloud mass and effective radius. In fact, unlike the previous two simulations, there is no obvious signature of the upper cloud in terms of mass loading in Fig. Having characterized the effects of the parameters that determine the photochemical parameterization in our simulations, we can now turn to the primary focus of this paper, which is an exploration of the effects of coalescence properties on the Venus cloud system. As in the first section of results, we will compare two simulations: one in which coagulation is allowed to proceed as normal, and a second in which coagulation is forbidden to occur. Then, unlike the earlier simulations, we also consider a third case in which we allow coalescence to occur for cloud droplets only when the environmental temperature is warmer than 283 K, a typical melting point for sulfuric acid under the atmospheric conditions experienced here  is comparable to the previous simulation. Finally, the condensational cloud region is almost completely devoid of involatile particles that can serve as cloud condensation nuclei (CCN). The CCN appear to have been almost entirely scavenged by the sulfuric acid droplets. This likely has contributed to the redistribution of volatile mass, as the larger number of potential activation sites results in a more even distribution of mass, hence smaller and more numerous droplets. Another consequence of this is that the larger number of cloud droplets overall results in a larger number of droplets able to reach higher altitude via eddy diffusion in our model, possibly providing a source for observed enhancements of sulfuric acid vapor at high altitudes , in addition to a simplified photochemistry parameterization and a binary homogeneous nucleation parameterization. In general, the simulated cloud in all cases is in good agreement with existing in situ and remote measurements of the Venus clouds.In the simulations looking only at the Condensational Cloud below 60 km, we find that a complete removal of the upper cloud boundary condition has only a minimal effect on the Condensational Cloud mass and particle size distributions. Hence, the Condensational Cloud is reasonably decoupled from the Photochemical Cloud on short timescales relative to those that govern the subcloud reservoir of the sulfuric acid.In the chemistry sensitivity tests, we found that there is a fairly small effect on the mass and particle sizes of the Condensational Cloud at low latitude; and a comparably larger effect at higher latitudes. However, this is possibly a result of the simplifying assumptions made in the photochemical production parameterization of the earlier chemistry-free simulations that are more consistent with the low latitude simulation than the high latitudes. That is, this difference likely tells us more about the inaccuracy of the high latitude 40–60 km simulations than the accuracy or inaccuracy of those simulations including chemistry. Future work will include a more realistic and interactive treatment of the relevant chemistry.In all cases, the total mass of the Photochemical Cloud is deficient relative to the observations. The current suite of simulations is insufficient to discriminate whether this is the result of errors in the chemistry assumptions, errors in the particle microphysics assumptions, or due to the neglect of the radiative-dynamical feedback in this suite of simulations.Temperature-dependent coagulation has been shown to have the potential to lead to a drastically different cloud distribution. While the range of mass loading, column abundance, and effective radius are all consistent with accepted bounds of previous observations, the specifics of the distributions do not appear to match previously retrieved estimates of variability. However, sensitivity to these parameters is demonstrated, and perhaps future improvements to the relevant microphysics will improve the predictions.The nature and distribution of the potential CCN is shown to be of significant importance to determining the cloud particle distribution. The effects of nucleation and activation are tremendous. Future study and characterization of the CCN are necessary to understand the clouds of Venus, perhaps from an in situ platform.Changes in the applied chemistry parameters sometimes led to model instability. This was usually driven by new particle formation and could be related to limitations of the assumed binary homogeneous nucleation parameterization used here. The author is aware of an ongoing effort to improve the binary homogeneous nucleation parameterization to wholly enclose the parameter space of the Venus atmosphere that contains aerosols . However, since the likelihood and process of heterogeneous nucleation depend strongly on the presence and composition of involatile particles in the cloud domain, these difficulties show that an improved characterization and understanding of the CCN are necessary for a complete understanding of the Venus cloud system.These simulations demonstrate that subtle changes in the properties of the aerosols that make up the Venus cloud system can have significant and measurable effects on the spatial distribution of the clouds. Many of the properties explored here are strong functions of particle composition. Since the composition of much of the constituents of the Venus clouds remain unconstrained, it is essential that in situ measurements be carried out in order to conclusively determine the composition of the aerosols in the Venus clouds.The existence of an enhanced number of particles having a large range of sizes in the temperature-dependent coagulation simulation is suggestive that conditions suitable for significant charge exchange among particles that is necessary for the onset of lightning are plausible.The observed changes can be very rapid: sometimes less than one day, but certainly exhibiting changes on scales of days to weeks. Future work will compare simulated radiances produced by these clouds to Akatsuki observations. This will enable further characterization of the structure and evolution of the Venus clouds. For example, flying an aerosol size and shape spectrometer to determine with improved spatial and size resolution the radii and habits of the Venusian aerosols will help resolve the ambiguity in the current state of understanding of the Venus cloud aerosol composition. Furthermore, such an instrument could prove insightful to the question of whether bacterial life might exist in the atmosphere of Venus, as suggested by Schulze-Makuch et al.  and Lima


The purpose of the study was to investigate the theoretical isometric point based of the curve of the femoral groove and relating it to the origin of the MPFL femoral tunnel on lateral radiograph by comparing a patellar instability cohort with a control cohort.From a Patellar Instability database the radiographs of 40 consecutive patients were analysed to define Schöttle’s point, and the arc of the circle of the trochlear groove. A comparison population of 20 radiographs from comparable patients with tibiofemoral joint disorders was used as a control. The distance from Schöttle’s point to the most anterior part of the groove (extension) was also compared to the distance to the distal end of the roof of the notch (flexion).The trochlea was circular in the controls but not the Patellofemoral Instability cohort where trochlear dysplasia is usually present. The difference between the extension and flexion length was a mean of − 2.0 ± 0.5 mm in the controls and + 6.0 ± 0.5 mm in the patellofemoral cohort. In neither cohort did the centre of the circle correspond to Schöttle’s point. The extension distance correlated with the boss height.The dysplastic trochlea is not circular and the centre of the best matched circle was different to the control trochleae which were circular. The circle centres did not correlate with Schöttle’s point for either cohort, and was more proximal in the Patellofemoral Instability cohort.For the MPFL to have equal tension throughout flexion within the groove, the length should not change. In normal knees the MPFL does not behave isometrically. The change in length, as measured from Schöttle’s point to the trochlea, was greater for patellofemoral instability patients explaining why an isolated MPFL reconstruction in the presence of severe trochlear dysplasia risks poor outcomes.Level of evidence III. Reconstruction of the medial patellofemoral ligament (MPFL) has become a popular operative strategy for managing recurrent patellar dislocation, for which a number of techniques have been described . The impThe problem with relying on anatomical landmarks for the origin of the MPFL is that all the work has, as stated above, been based on normal knees. However, the path of the patella during knee flexion changes completely in the presence of trochlear dysplasia (TD) as the proximal part of the groove is anterior to the path of the normal groove. It is logical to expect that the more severe the dysplasia the further from the norm the patellar movement will be and the more anisometric an MPFL reconstruction will be if the standard femoral tunnel position is chosen. This has been confirmed clinically in that MPFL reconstruction alone does not work well in patients with significant TD , 11, 12.The purpose of this study was to identify the radiographical “isometric point” of the trochlea from a cohort of patients presenting with patellar instability and compare this in a control population with tibiofemoral disorders and also with a recognised femoral tunnel position, the Schöttle’s point . The hypPatients with recurrent patellar dislocation were identified from the institution’s Bluespier Data Management software ; within it is a dedicated Patellofemoral Database. From this, the first 40 patients with perfect pre-operative lateral plain radiographs  were selected. The plain radiographs were stored on the hospital Picture Archiving Computer System (PACS) using the standard measurement tools available on the PACS software (Fuji Synapse). This cohort was called the PFI  cohort. The patients’ basic demographics were; mean age was 26-years-old (range 17–61-years-old), gender 19 male and 21 female, side 21 right and 19 left.A comparison Control cohort was identified from patients presenting to a Knee Clinic and selected for arthroscopic surgery for tibiofemoral disorders; ACL reconstruction or meniscal repair. Twenty consecutive patients were selected and images retrieved as above. The mean age was 26-years-old (range 15–42), 11 were male and 9 female, with 12 right knees and 8 left.The radiographical analysis began by identifying the femoral tunnel position as defined by Schöttle  and markOne author (Observer 1) undertook the measurements. Twenty patients were then randomly selected and the same author repeated the measurements 1 week later. These 20 were also analysed by a second author (Observer 2). The comparison cohort observations were undertaken by Observer 2.Radiographic review does not require ethical approval in the UK. The research database has approval for use for research purposes and report writing by the Research and Development Department reference number 2011ORTH09L (142-10-11).t test using Wizard for Mac version 1.8.16 since the data were continuous and normally distributed (confirmed by Shapiro–Wilk test) Comparisons were analysed between control and study cohorts. Simple regression analysis was undertaken for correlations between boss height and vertical or horizontal offset for both cohorts combined. Statistical significance was set at p = 0.05.The data were collected and stored on an Excel spreadsheet. Inter- and intra-observer differences were analysed as means and standard deviations. These data were compared by In all the parameters there were no statistically significant differences between the observers or within an observer  but was for the horizontal offset  where the greater the boss height the more proximal the trochlear isometric point compared to controls. However the difference in length between AB and AD in the cohorts correlated to the boss height .No correlation was found between boss height and the vertical offset  does not correspond to the femoral origin of the MPFL with normal controls having the isometric point on average more distal, whereas in the dysplastic group the point tended to be proximal. The more severe the dysplasia, the more anterior the isometric point was relative to Schöttle’s point Fig. . FurtherSince the origin of the MPFL does not match the isometric point in normal trochleae, then the MPFL cannot behave isometrically through the range of knee motion in the normal knee. This is well recognised; the ligament slackens in flexion where the patella is “captured” by the depth of the groove and the MPFL is not required to act as a check rein and stop lateral displacement . The difIt was noticeable that when applying a circle to the groove line in the PFI cohort, the circle could be placed to touch two points on the groove, e.g., B and D Fig.  or the cZiegler et al.  emphasisThe assumption in this study is that, in the sagittal plane, the path of the patella is defined by the shape of the trochlea, and that the patella is at a normal height. Given that the trochlea is highly variable in patients with patellar dislocation since the majority have TD, then this explains why significant TD is a risk factor for failure of isolated MPFL reconstruction . Having The strengths of this study are that the analysis of the groove on lateral radiograph can be performed in a standard clinic. However, it does not give an accurate guide to the tunnel position down to the level of millimetres, nor is it desirable to define a precise tunnel position radiographically pre-operatively as the final position is decided intra-operatively. However the surgeon can use this analysis to decide whether an isolated MPFL reconstruction is a sensible option by noting the severity of any TD and consider how the graft length may change during knee flexion based on the shape of the trochlea. It also shows that the at-risk patient group with patellofemoral instability are different anatomically from the normal and that laboratory studies that use normal cadaveric knees , 26 cannThis study did not consider the patellar insertion of the MPFL. The effect of patellar height on the MPFL length has been analysed in a computer model . This foFor the MPFL to have equal tension throughout flexion within the groove, the length should not change. In normal knees the MPFL does not behave isometrically. The change in length, as measured from Schöttle’s point, was greater for patellofemoral instability patients explaining the finding that an isolated MPFL reconstruction in the presence of severe trochlear dysplasia is contraindicated.The centre of the circle formed from the trochlea on lateral plain radiograph was different between control patients and those with patellofemoral instability and did not correlate with the origin of the MPFL as defined by Schöttle’s point for either cohort. The MPFL in the normal knee does not have equal tension throughout flexion but the length change was greater for patellofemoral instability patients and was greatest for those with a boss height ≥ 5 mm. Biomechanical data on the MPFL related to the femoral tunnel position from normal cadavers does not correspond to the patient population at risk of an MPFL reconstruction.


Background and purpose — Idiopathic clubfeet are commonly treated with serial manipulation and casting, known as the Ponseti method. The use of Plaster of Paris as casting material causes both exothermic and endothermic reactions. The resulting temperature changes can create discomfort for patients.Patients and methods — In 10 patients, we used a digital thermometer with a data logger to measure below-cast temperatures to create a thermal profile of the treatment process.minT = 26 °C) that lasted 12 hours.Results — After the anticipated temperature peak, a surprisingly large dip was observed (Interpretation — Evaporation of excess water from a cast might be a cause for discomfort for clubfoot patients and subsequently, their caregivers. The common treatment of idiopathic clubfoot  consists of serial manipulation and casting, known as the Ponseti method Ponseti . The treThe Ponseti method dictates toe-to-groin casts with the knee flexed to prevent slipping of the cast Ponseti . PlasterBandage rolls impregnated with PoP are soaked in lukewarm water before being wrapped around the foot. The PoP has an exothermic chemical reaction with water. Many studies have focused on the extent of the generated heat and the effects of the associated temperature peak, which appears minutes after application  was used to measure the temperature under the cast. The accuracy of the sensor is ±0.5 °C  was used between the skin and the thermometer and wires . The theThe cast technician cut 1 roll of Gypsona  in half, dipped it in a sink filled with lukewarm (20–25 °C) water and applied it to the clubfoot while the orthopedist maintained the position of the foot. Care was taken not to use more than 3 layers of cast tape. Wires were routed distally and, as soon as the plaster had set, the casing was attached to the cast laterally with a single layer of Peha-haft bandage  . ParentsAt the next scheduled weekly meeting the cast and thermometer were removed. While the parents bathed their child, the sensors were left in a stable position for at least 15 minutes for calibration after which the data were copied to a computer and the battery replaced. The foot was carefully inspected for any signs of skin damage and the protocol was repeated until the final cast before tenotomy.The same measurement protocol was used to cast 1 rubber clubfoot model . The weight of all components was documented and the total weight of the rubber foot plus cast was monitored for several days. This provided an estimation of the excess water content in the plaster cast and the time it takes to evaporate.Q = m·ΔHev, with m the measured mass of the excess water and ΔHev(25 °C) = 2,442 J/g (Rajput The latent heat of evaporation of water is described as g Rajput .The system was programmed to store time and temperature data continuously (0.16 Hz) for the first 4 hours, after which the system entered a low power state (85 µA) to save battery power. 4 times per hour it woke from this state to collect data for 10 seconds. Each 10 s period resulted in 2 temperature measurements over which the average was taken. The system featured a button to wake up after the cast was removed.medfilt1 (Pratt 0t) was defined as the moment the plaster cast touched the foot. The height of the temperature peak (maxT) was calculated as the maximum value over the first 3 hours, the final equilibrium temperature (endT) as the mean value over the final 3 days of measurement, and the lowest temperature (minT) as the minimum value after maxT.Data was processed using Matlab version R2016b. Potential sensor errors were filtered using the median filter t1 Pratt . The staendT. The moment the temperature reached a value within 1 standard deviation of endT was defined as the end of the temperature dip.The beginning of the temperature dip was defined as the moment the temperature reached a value smaller than 1 standard deviation of max, TminT and endT) were tested for normality using the Shapiro-Wilk test. The Student t-tests were used to test the difference between temperatures for statistical significance.The 3 sets of temperature data , and therefore did not require their approval (document number M16.196266). After obtaining informed written consent from both parents, the children were included in the study. Financial support was provided by Stichting voor de Technische Wetenschappen [grant P12-03]. No competing interests declared.Complications in the form of pressure marks were encountered in 4 cases. In 2 of those cases further measurements were canceled but the data obtained were included for analysis.Technical malfunctioning occurred in 5 measurements . 29 successful measurements were performed on 10 clubfeet, giving more than 3,000 hours of data.The measurement with a clubfoot model showed that approximately 35 g of water was used for one roll of PoP bandage of 75 g. Over the course of 2 days the water content in the cast decreased to reach an equilibrium of 14 g. This means that 14 g of the original water content attached to the PoP to form hard gypsum and the remaining 21 g of excess water evaporated. This ratio fits well within the molecular ratio of the chemical reaction, which also predicts the generation of 740 kJ of heat . The reqmaxT). None of the below-cast temperatures ever exceeded 40 °C and no thermal injuries were observed (All temperature measurements showed a clear temperature peak after the application of the plaster cast (observed .endT).After the peak, a decrease to a lower temperature was observed (p < 0.001) . On averAll 3 sets of temperature data were normally distributed . There wThis is the first study to present long-term temperature measurements underneath the cast in the treatment of clubfeet. A surprisingly large temperature dip was observed caused by the evaporation of excess water. In several cases temperatures as low as 22 °C were observed and they stayed low for more than 12 hours.Our measurements showed a temperature peak after 9 minutes . BSN MedImmediately after reaching the peak, the cast started to cool. This is also visible in BSN Medical’s measurement in which the temperature drops below the ambient temperature after approximately 1 hour . DependiIn adults, 1 case study exists which describes observed hypothermia after the application of a plaster jacket for immobilization of the cervical spine Vale . CaregivIt would take 51 kJ to evaporate the excess water of 1 cast. Part of this energy will be extracted from the environment, but a substantial part of it must be produced by the child. However, the thermoregulatory system of newborns is not yet fully developed, and they experience great difficulties when facing a cold environmental challenge (Pierro et al. A newborn’s total energy expenditure in the first month after birth is 1.0–1.3 MJ/day FAO . Up to 8Given that newborns are naturally well monitored by their parents, that hypothermia in newborns is easily detected, and that no such case studies exist for clubfoot, it is unlikely that casting induces severe or moderate hypothermia. Still, having cold feet for half a day undoubtedly is uncomfortable and plausibly affects the newborn’s mood.We acknowledge limitations of our study. First, we did not measure whether the wet and cold casts affect the child’s core temperature. If they do, a more prominent effect would be expected in bilateral cases. However, the number of children in our study does not allow for any meaningful test for subgroup differences, and no trend could be identified.Second, the sensors were placed on the skin on the plantar aspect of the foot. So the measurements reflect only the temperature of that part of the foot and not the core temperature of the patient. Hypothermia was neither measured nor diagnosed based on clinical symptoms. Future research should include measuring the core temperature during the first 24 hours after casting to study the possibility of casting-induced hypothermia.So far only anecdotal information exists regarding cold clubfeet (Bridgens and Kiely Preventing a clubfoot from getting cold would be possible if less excess water needed to be evaporated. However, squeezing the water out of the plaster to use less water results in hotter plaster and increased risk of burns: the excess water is needed to release the heat from the exothermic reaction Kaplan .Using synthetic cast tape as an alternative casting material could be a viable option to decrease the discomfort of cold feet. The chemical reaction and the structure of the material both cause the drying process to be shorter than when using PoP.In summary, after an anticipated temperature peak, a surprisingly large temperature dip was observed. More research is needed to assess whether the Ponseti method affects the child’s core temperature.The authors would like to thank the parents of all participants for their trust and patience, and the medical staff of the Gipskamer for all their help and advice. Special thanks are offered to Maaike Vos, Els Huizenga, and Rohan Choudhari for performing the measurements.RG conceived and designed the experiments, performed the experiments, analyzed the data, and wrote the paper. EH and GV critically edited and reviewed the test protocol, data interpretation, and the manuscript. PM performed the experiments, critically edited and reviewed the test protocol, data interpretation, and the manuscript.Acta thanks Naomi Davis and Henrik Wallander for help with peer review of this study.


MC) toolkits for patient‐specific dose simulation and perform analysis and plan comparisons for double‐scattering proton therapy systems. The authors aim to fill two aspects of this process previously not explicitly published. The first one addresses the modeling of field‐specific components in simulation space. Patient‐specific compensator and aperture models are exported from treatment planning system and converted to STL format using a combination of software tools including Matlab and Autodesk's Netfabb. They are then loaded into the MC geometry for simulation purpose. The second details a method for easily visualizing and comparing simulated doses with the dose calculated from the treatment planning system. This system is established by utilizing the open source software 3D Slicer. The methodology was demonstrated with a two‐field proton treatment plan on the IROC lung phantom. Profiles and two‐dimensional (2D) dose planes through the target isocenter were analyzed using our in‐house software tools. This present workflow and set of codes can be easily adapted by other groups for their clinical practice.The methods described in this paper allow end users to utilize Monte Carlo ( The first provides a detailed workflow for the creation of 3D models for field‐specific components, which can be imported into the simulation geometry for double‐scattering systems. The second describes the steps of visualization and comparison of doses generated by MC toolkits and treatment planning system.To start the simulation, we have first modeled our proton machine in TOPAS and benchmarked against measured commissioning beam data.2.AThe information necessary to define each compensator was expressed though several tags in the RN Plan file. Specifically, the size of the compensator was given by the corner position, number of rows, number of columns, and pixel dimensions, and the thickness was given as a dimensionless 2D array. The method, detailed in the Appendix When inserting the device models into the beam line geometry, the size of the compensator needed to be scaled to their actual size determined through its position in the beam line as shown in Fig. 2.BWhereas the compensator is defined as an array of thicknesses, the aperture shape was given as a series of coordinates defining perimeter of the cutout region. These coordinates were reshaped and then scaled with Eq. A grid was defined with the dimensions of the aperture and assigned values of 1 if the position in the grid is inside of a circle defining the outer edge of the aperture and outside of the coordinates defining the aperture. This grid was converted to an STL file with the same method as the compensator Appendix . Because2.CBoth TOPAS (version 3.1.p2) and Geant4 (version 10.3) score the calculated dose values from each simulation onto a preset calculation grid. Geant4 saves the dose with a series of copyids, and TOPAS has the added functionality of saving the results as a DICOM RTDose file. In both cases additional software is required to display the dose and perform quantitative analysis. There are a number of tools which can be helpful for the purpose of evaluating and comparing doses.Doses generated in TOPAS and saved as DICOM RT Dose files need only to be normalized and have the position corrected before they were loaded directly into 3D Slicer.The raw value for the simulated dose in each voxel corresponds with the total number of incident particle initiated for each run, while the values from a commercial treatment planning software are normalized to the prescription value. To be able to compare them side by side, we utilized the DICOM tag “Dose Grid Scaling”. The dose at a particular position is given by the value for the voxel in the dose grid multiplied by the dose grid scaling, so normalization was achieved through multiplying the “Dose Grid Scaling” tag by the ratio of the dose at isocenter in the TPS and MC. A median filter was also applied for the simulated dose grid to account for noise in the simulation dose before comparing to the treatment planning values.Another useful tool in radiotherapy is acquiring dose profiles. This functionality is acquired through the simultaneous use of both 3D Slicer and Matlab. First the coordinates of the desired profile were found in 3D Slicer. Then these coordinates are then converted to voxel locations, and a profile was plotted in Matlab.The output files from Geant4 simulations require an additional step to process. This step was done through converting the copyids into coordinates in a 4‐dimensional (4D) dose array Appendix . Additio315 The phantom is composed of tissue, lung, bone, and heart equivalent material, and has a target in the center which moves during treatment delivery. To account for the motion a 4D CT scan was done with our CT Discovery using the Varian RPM system. A treatment was plan with two fields was made using the maximum intensity projection from the 4D scan to delineate the target. The compensators and apertures were converted to STL format and were shown with Netfabb in Figs. 8 initial proton particles were used and the computing time lasts from 2 to 3 h.The procedure described above was performed on an example case using the IROC lung phantom.Normalized‐ and filtered‐simulated doses and Eclipse‐calculated doses were then loaded into 3D Slicer. The dose from each was shown side by side in Fig. The TOPAS‐simulated doses and Eclipse‐calculated doses were compared with the film placed through each plane of the target in the IROC phantom. Gamma analysis of the films was performed by IROC with criteria of 7% and 5 mm. IROC uses this criteria to account for the effects of film quenching.4https://www.mathworks.com/matlabcentral/fileexchange/68660-toolkits-for-monte-carlo-dose-simulation-and-visualizationIn this paper we detail procedures for modeling treatment field‐specific components and performing MC simulation for double‐scattering proton therapy system previously unpublished. This procedure also allows for users to easily evaluate and compare the doses between commercial treatment planning software and MC simulations. All Matlab code used in this publication is available freely so other in the community can use these methods. It can be found at The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or nonfinancial interest in the subject matter or materials discussed in this manuscript.