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Background Detailed visualization of the lymphatic vessels would greatly assist in the diagnosis and monitoring of lymphatic diseases and aid in preoperative planning of lymphedema surgery and postoperative evaluation. Purpose To evaluate the usefulness of photoacoustic imaging (PAI) for obtaining three-dimensional images of both lymphatic vessels and surrounding venules. Materials and Methods In this prospective study, the authors recruited healthy participants from March 2018 to January 2019 and imaged lymphatic vessels in the lower limbs. Indocyanine green (5.0 mg/mL) was injected into the subcutaneous tissue of the first and fourth web spaces of the toes and below the lateral malleolus. After confirmation of the lymphatic flow with near-infrared fluorescence (NIRF) imaging as the reference standard, PAI was performed over a field of view of 270 × 180 mm. Subsequently, the number of enhancing lymphatic vessels was counted in both proximal and distal areas of the calf and compared between PAI and NIRF. Results Images of the lower limbs were obtained with PAI and NIRF in 15 participants (three men, 12 women; average age, 42 years ± 12 [standard deviation]). All participants exhibited a linear pattern on NIRF images, which is generally considered a reflection of good lymphatic function. A greater number of lymphatic vessels were observed with PAI than with NIRF in both the distal (mean: 3.6 vessels ± 1.2 vs 2.0 vessels ± 1.1, respectively; P < .05) and proximal (mean: 6.5 vessels ± 2.6 vs 2.6 vessels ± 1.6; P < .05) regions of the calf. Conclusion Compared with near-infrared fluorescence imaging, photoacoustic imaging provided a detailed, three-dimensional representation of the lymphatic vessels and facilitated an increased understanding of their relationship with the surrounding venules. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Lillis and Krishnamurthy in this issue.

IntroductionPhotoacoustic technology can be used for non-invasive imaging of blood vessels. In this paper, we report on our prototype photoacoustic imaging system with a newly designed ultrasound sensor and its visualization performance of microvascular in animal.MethodsWe fabricated an experimental system for animals using a high-frequency sensor. The system has two modes: still image mode by wide scanning and moving image mode by small rotation of sensor array. Optical test target, euthanized mice and rats, and live mice were used as objects.ResultsThe results of optical test target showed that the spatial resolution was about 2 times higher than that of our conventional prototype. The image performance in vivo was evaluated in euthanized healthy mice and rats, allowing visualization of detailed blood vessels in the liver and kidneys. In tumor-bearing mice, different results of vascular induction were shown depending on the type of tumor and the method of transplantation. By utilizing the video imaging function, we were able to observe the movement of blood vessels around the tumor.ConclusionWe have demonstrated the feasibility of the system as a less invasive animal experimental device, as it can acquire vascular images in animals in a non-contrast and non-invasive manner.

Lymphedema occurs when interstitial fluid and fibroadipose tissues accumulate abnormally because of decreased drainage of lymphatic fluid as a result of injury, infection, or congenital abnormalities of the lymphatic system drainage pathway. An accurate anatomical map of the lymphatic vasculature is needed not only for understanding the pathophysiology of lymphedema but also for surgical planning. However, because of their limited spatial resolution, no imaging modalities are currently able to noninvasively provide a clear visualization of the lymphatic vessels. Photoacoustic imaging is an emerging medical imaging technique that provides unique scalability of optical resolution and acoustic depth of penetration. Moreover, light-absorbing biomolecules, including oxy- and deoxyhemoglobin, lipids, water, and melanin, can be imaged. Using exogenous contrast agents that are taken up by lymphatic vessels, e.g., indocyanine green, photoacoustic lymphangiography, which has a higher spatial resolution than previous imaging modalities, is possible. Using a new prototype of a photoacoustic imaging system with a wide field of view developed by a Japanese research group, high-resolution three-dimensional structural information of the vasculatures was successfully obtained over a large area in both healthy and lymphedematous extremities. Anatomical information on the lymphatic vessels and adjacent veins provided by photoacoustic lymphangiography is helpful for the management of lymphedema. In particular, such knowledge will facilitate the planning of microsurgical lymphaticovenular anastomoses to bypass the excess fluid component by joining with the circulatory system peripherally. Although challenges remain to establish its implementation in clinical practice, photoacoustic lymphangiography may contribute to improved treatments for lymphedema patients in the near future.

Objective Aging is one of the causes of primary lymphedema. However, the effects of aging on the lymphatic system are still not completely understood. We investigated the effects of aging on the lymphatic vessels in the lower extremities of healthy volunteers using photoacoustic imaging. Methods Healthy volunteers who underwent photoacoustic lymphangiography between March 2018 and January 2019 were enrolled. To visualize lymphatics, indocyanine green (ICG, 5.0 mg/mL) was injected subcutaneously into the first and fourth web spaces of the foot and under the lateral malleolus. Subsequently, near-infrared fluorescence lymphography was performed to confirm good ICG flow, and photoacoustic lymphangiography was performed on the medial side of the lower leg. Ti sapphire laser irradiation at 797 and 835 nm, the optimal wavelengths for visualizing ICG and blood, was applied. The number of lymphatic vessels shown at areas 10 cm (L10) and 20 cm (L20) cranially from the internal malleolus was counted. Results Nineteen healthy volunteers (4 males and 15 females) were enrolled in the study. Their mean age was 42.9 ± 12.8 years. One volunteer was bilaterally imaged; 15 left lower limbs and 5 right lower limbs were imaged. The number of lymphatic vessels visualized increased with age. There were strong positive correlations between age and L10 (R = 0.729, P Conclusions Photoacoustic imaging indicates that the number of lymphatic vessels increases with age. Lymphatic stasis resulted in visualization of not only normal drainage pathways but also nonfunctional lymphatic pathways.

Supplemental Digital Content is available in the text., Summary: It is difficult to evaluate the postoperative patency of lymphaticovenular anastomosis, but this evaluation is essential for determining surgical results. When using the current standard modality, near-infrared fluorescent lymphography, it is difficult to observe patency if the anastomotic point is veiled by dermal backflow. In this study, we used a new photoacoustic imaging device, PAI-05, to check the patency of anastomosis. We performed photoacoustic lymphangiography after lymphaticovenular anastomosis surgery. By digitally subtracting the superficial area, we can examine an area deeper than the dermal backflow, which is not visible by near-infrared fluorescent lymphography. The connection between the lymphatic vessel and the venule observed in the image is an indication of the patency of anastomosis. However, in a non-patent anastomosed site, the lymphatic vessel has a gap that separates it from the venule at the anastomosed site. Although photoacoustic lymphangiography cannot be used to visualize the lymphatic vessels that are not contrasted by indocyanine green, the resulting high-resolution images and clear anastomosis evaluation afforded by it will contribute to the development of future lymphedema treatments.

Supplemental Digital Content is available in the text.

The anatomical design of the human foot is considered to facilitate generation of bipedal walking. To clarify the morphofunctional mechanisms of the human foot, efforts have been made to directly c...

OBJECT Extended endoscopic transnasal surgeries for skull base lesions have recently been performed. Some expert surgeons have attempted to remove tumors such as chordomas, meningiomas, and pituitary adenomas in the clival region using the transnasal approach and have reported abducens nerve injury as a common complication. There have been many microsurgical anatomical studies of the abducens nerve, but none of these studies has described an anatomical landmark of the abducens nerve in the transnasal approach. In this study the authors used cadaver dissections to describe Grüber's ligament as the most reliable landmark of the abducens nerve in the transnasal transclival view. METHODS The petroclival segment of the abducens nerve was dissected in the interdural space—which is also called Dorello's canal, the petroclival venous gulf, or the sphenopetroclival venous confluence—using the transnasal approach in 20 specimens obtained from 10 adult cadaveric heads. RESULTS The petroclival segment of the abducens nerve clearly crossed and attached to Grüber's ligament in the interdural space, as noted in the transnasal view. The average length of the dural porus to the intersection on the abducens nerve was 5.2 ± 1.0 mm. The length of the posterior clinoid process (PCP) to the intersection on Grüber's ligament was 6.4 ± 2.6 mm. The average width of Grüber's ligament at the midsection was 1.6 ± 0.5 mm. CONCLUSIONS Grüber's ligament is considered a useful landmark, and it is visible in most adults. Thus, surgeons can find the abducens nerve safely by visualizing inferolaterally along Grüber's ligament from the PCP.

Limited clinical evidence demonstrates the effectiveness of direct retroperitoneal pelvic packing for hemorrhage control in pelvic fractures due to the difficulty in measuring pressure on the pelvic walls within the pelvic cavity after retroperitoneal pelvic packing. Using a cadaver model, the authors aimed to assess whether retroperitoneal pelvic packing generates pressure that exceeds the venous return and arterial pressure in the pelvis. The pressure on the pelvic wall was measured in 5 fresh Japanese cadavers. Sensors were placed at 4 points on the pelvic wall, and the pressure at each point was measured after the insertion of each of 3 sponges, per the procedure originally described for direct retroperitoneal pelvic packing. In each specimen, the average pressure across all 4 points on the pelvic wall increased with the addition of each sponge, reaching 12.3±4.5 mm Hg when all 3 sponges were inserted. Furthermore, the pressure at the pelvic floor and posterior pelvic brim increased significantly, whereas the pressure at the anterior and middle pelvic brim increased nonsignificantly. The results of this study suggest that retroperitoneal pelvic packing provides pressure on the pelvic wall that exceeds the venous pressure and is thus effective for the control of venous hemorrhage in pelvic fractures. Currently, the recommended procedure combines external fixation for venous bleeding, transcatheter arterial embolization, and pelvic packing; however, the authors' results suggest that pelvic packing alone may be effective for controlling venous hemorrhage in pelvic fracture. [ Orthopedics. 2017; 40(6);e947–e951.]

We propose a fully automatic system to reconstruct and visualize 3D blood vessels in Augmented Reality (AR) system from stereo X-ray images with bones and body fat. Currently, typical 3D imaging technologies are expensive and carrying the risk of irradiation exposure. To reduce the potential harm, we only need to take two X-ray images before visualizing the vessels. Our system can effectively reconstruct and visualize vessels in following steps. We first conduct initial segmentation using Markov Random Field and then refine segmentation in an entropy based post-process. We parse the segmented vessels by extracting their centerlines and generating trees. We propose a coarse-to-fine scheme for stereo matching, including initial matching using affine transform and dense matching using Hungarian algorithm guided by Gaussian regression. Finally, we render and visualize the reconstructed model in a HoloLens based AR system, which can essentially change the way of visualizing medical data. We have evaluated its performance by using synthetic and real stereo X-ray images, and achieved satisfactory quantitative and qualitative results.

In this paper, we focus on semi-supervised learning for biomedical image segmentation, so as to take advantage of huge unlabelled data. We observe that there usually exist some homogeneous connected areas of low confidence in biomedical images, which tend to confuse the classifier trained with limited labelled samples. To cope with this difficulty, we propose to construct forest oriented super pixels(voxels) to augment the standard random forest classifier, in which super pixels(voxels) are built upon the forest based code. Compared to the state-of-the-art, our proposed method shows superior segmentation performance on challenging 2D/3D biomedical images. The full implementation (based on Matlab) is available at https://github.com/lingucv/ssl_superpixels.

The development of animal models that mimic human allergic responses is crucial to study the pathophysiology of disease and to generate new therapeutic methodologies. Humanized mice reconstituted with human immune systems are essential to study human immune reactions in vivo and are expected to be useful for studying human allergies. However, application of this technology to the study of human allergies has been limited, largely because of the poor development of human myeloid cells, especially granulocytes and mast cells, which are responsible for mediating allergic diseases, in conventional humanized mice. In this study, we developed a novel transgenic (Tg) strain, NOD/Shi-scid-IL2rγnull (NOG), bearing human IL-3 and GM-CSF genes (NOG IL-3/GM–Tg). In this strain, a large number of human myeloid cells of various lineages developed after transplantation of human CD34+ hematopoietic stem cells. Notably, mature basophils and mast cells expressing FcεRI were markedly increased. These humanized NOG IL-3/GM–Tg mice developed passive cutaneous anaphylaxis reactions when administered anti–4-hydroxy-3-nitrophenylacetyl IgE Abs and 4-hydroxy-3-nitrophenylacetyl. More importantly, a combination of serum from Japanese cedar pollinosis patients and cedar pollen extract also elicited strong passive cutaneous anaphylaxis responses in mice. Thus, to our knowledge, our NOG IL-3/GM–Tg mice are the first humanized mouse model to enable the study of human allergic responses in vivo and are excellent tools for preclinical studies of allergic diseases.

Hypothesis The clavicle serves as a strut between the thorax and scapula, and lack of this function could affect shoulder mobility. We hypothesized that clavicular discontinuity changes shoulder kinematics, particularly affecting scapular motion. Materials and methods The study used 14 cadaveric shoulders. Cadavers were stabilized in the sitting position. Manual elevation in the sagittal, scapular, and coronal planes was performed in the intact and clavicular discontinuity models. The thorax-scapula distance and 3-dimensional scapular motion during shoulder elevation were recorded using an electromagnetic tracking device. The differences between the 2 experimental models at each position were analyzed. Results Clavicular discontinuity resulted in a decreased thorax-scapula distance and in reduced external rotation, upward rotation, and posterior tilting of the scapula. The kinematic changes were observed during elevations in all 3 planes but were greatest in the sagittal plane compared with the scapular and coronal planes. Conclusions The findings of this study revealed that discontinuity of the clavicle affects shoulder kinematics. Because of its anatomic shape and position, the clavicle stabilizes the external, upward, and posterior rotation of the scapula during arm movement. This function of the clavicle may assist glenohumeral joint motion and help prevent subacromial impingement.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, whose pathology is characterized by death of upper and lower motor neurons, inclusion bodies in remaining neurons and glia, and glial activation around the neurons. The pathophysiological mechanisms underlying ALS are multifactorial and remain to be fully elucidated. Here, we review d-serine-related findings in ALS and delineate how d-serine metabolism is disturbed and why such d-serine derangement could potentially be toxic to motoneurons.

The precise venous anatomy of the glabellar to the forehead region remains unknown. This study aimed to detail the venous architecture of the glabellar region to the forehead in conjunction with that of the supratrochlear artery to reduce the risk of venous congestion of flaps in this area. Fifteen fresh human cadavers were examined here. In five specimens, contrast medium was injected only into the venous system; in 10 specimens, two different types of contrast media were injected into the arterial and venous systems, respectively. A total of 30 hemifacial specimens were radiographed stereoscopically and observed microscopically. In all the cadavers, a distinct vein (termed as the "transverse nasal root vein") connected the bilateral angular veins. One or two large ascending veins branched from the transverse nasal root or angular vein, coursing toward the forehead skin. Numerous small veins branched out from the large ascending vein(s), forming a subdermal polygonal venous network. Small ascending veins arose from this network and coursed toward the dermis, draining venous flow from the dermis. Three different-sized valves prevented the reflux of blood in the venous pathway. The large ascending vein(s) and supratrochlear artery ran parallel only in the medial canthal area. Tiny venous vasa vasorum surrounded the adventitia of the supratrochlear artery and anastomosed with the polygonal venous network, while a few small veins from the vasa vasorum ascended toward the dermis. Understanding the venous architecture of this region is expected to facilitate the safe elevation of various flaps in the area.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that affects millions of patients worldwide. The current disease-modifying therapies (DMTs) that are widely used to treat MS only show modest effects. Because MS is a chronic disease, it is important to develop treatments that have better long-term efficacy. Recently, several new-generation DMTs have been developed, most of which target specific immune molecules based on the assumption that MS is an autoimmune disease. These DMTs are designed to inhibit inflammation that is thought to directly cause demyelination. Preliminary studies suggest that these new therapies are likely to show a greater effect in reducing relapses in early MS patients, although their long-term efficacy is still unknown. In contrast, it was recently reported that the initial course of MS does not significantly influence long-term disability and that disability increases approximately at the same rate despite variable relapse frequencies. Furthermore, new neuropathological evidence now argues against the autoimmune hypothesis and suggests that MS is a primary oligodendrogliopathy disease in which the inflammatory response may be a mere epiphenomenon. So can we be optimistic about the unproven long-term outcomes of new DMTs or should we reconsider the pathogenesis of MS when developing more disease-specific treatments?

Background Quantifying detailed 3-dimensional (3D) kinematics of the foot in contact with the ground during locomotion is crucial for understanding the biomechanical functions of the complex musculoskeletal structure of the foot. Biplanar X-ray fluoroscopic systems and model-based registration techniques have recently been employed to capture and visualise 3D foot bone movements in vivo, but such techniques have generally been performed manually. In the present study, we developed an automatic model-registration method with biplanar fluoroscopy for accurate measurement of 3D movements of the skeletal foot. Methods Three-dimensional surface models of foot bones were generated prior to motion measurement based on computed tomography. The bone models generated were then registered to biplanar fluoroscopic images in a frame-by-frame manner using an optimisation technique, to maximise similarity measures between occluding contours of the bone surface models with edge-enhanced fluoroscopic images, while avoiding mutual penetration of bones. A template-matching method was also introduced to estimate the amount of bone translation and rotation prior to automatic registration. Results We analysed 3D skeletal movements of a cadaver foot mobilized by a robotic gait simulator. The 3D kinematics of the calcaneus, talus, navicular and cuboid in the stance phase of the gait were successfully reconstructed and quantified using the proposed model-registration method. The accuracy of bone registration was evaluated as 0.27 ± 0.19 mm and 0.24 ± 0.19° (mean ± standard deviation) in translation and rotation, respectively, under static conditions, and 0.36 ± 0.19 mm and 0.42 ± 0.30° in translation and rotation, respectively, under dynamic conditions. Conclusions The measurement was confirmed to be sufficiently accurate for actual analysis of foot kinematics. The proposed method may serve as an effective tool for understanding the biomechanical function of the human foot during locomotion.

Amyloid beta (Abeta) is closely related to the onset of Alzheimer's disease (AD). To construct AD animal models, a bolus administration of a large dose of toxic Abeta into the cerebral ventricles of rodents has been performed in earlier studies. In parallel, a continuous infusion system via an osmotic pump into the cerebral ventricle has been developed to make a rat AD model. In this study, we developed a mouse AD model by repetitive administration of Abeta25-35 via a cannula implanted into the cerebral ventricle. Using this administration system, we reproducibly constructed a mouse with impaired spatial working memory. In accordance with the occurrence of the abnormal mouse behavior, we found that the number of choline acetyltransferase (ChAT)-positive neurons was reduced in paraventricular regions of brains of Abeta25-35-administered mice in a dose-dependent manner. Considering that the repetitive administration of a small dose of toxic Abeta via an implanted cannula leads to a brain status more resembling that of the AD patients than a bolus injection of a large dose of Abeta, and therapeutic as well as toxic agents are able to be repeatedly and reliably administered via an implanted cannula, we concluded that the implanted cannula-bearing AD mouse model is useful for development of new AD therapy.

The subcutaneous adipofascial tissue over the entire body was radiographically and macroscopically investigated in 20 fresh and embalmed cadavers. The subcutaneous adipofascial tissue was made up of two adipofascial layers. Because the superficial layer forms a solid structure and is thought to protect against external forces, the adipofascial system formed by the solid structure was named the "protective adipofascial system (PAFS)". Because the deep layer forms a mobile layer and is thought to lubricate musculoskeletal movement, the adipofascial system formed by the mobile structure was named "lubricant adipofascial system (LAFS)". By classifying subcutaneous adipofascial tissue by its functional characteristics, we found we could understand the subcutaneous adipofascial structure over the entire body well.

Anatomy of the superficial temporal artery and vein was analyzed with arteriograms, venograms, and arteriovenograms of fresh cadavers that had been injected with contrast medium. The superficial temporal artery always divided into two major branches: the frontal and parietal branches. However, the superficial temporal vein divided into one, two, or three major branches. The distribution area of the major branches of the superficial temporal vein was larger than that of major branches of the superficial temporal artery, and arteriovenograms clearly demonstrated that, except for its proximal portion, the superficial temporal vein was independent of the superficial temporal artery. The frontal and parietal branches of the superficial temporal artery had thin venae comitantes that originated from the proximal portion of the superficial temporal vein, and the venae comitantes gave off branches toward the skin and the underlying soft tissue. Branches to the skin anastomosed with a superficial venous network in the skin layer, which was formed by ramifications of the superficial temporal vein. The venous architecture of the temporal and parietal regions consisted of cutaneous veins and venae comitantes and was basically similar to that of the forearm and scapular region.

OBJECTIVE: The goals of this investigation were to perform a detailed analysis of petroclival microanatomic features, to investigate the course of the abducens nerve in the petroclival region, and to identify potential causes of injury to neurovascular structures when anterior transpetrosal or transvenous endovascular approaches are used to treat pathological lesions in the petroclival region. METHODS: Petroclival microanatomic features were studied bilaterally in seven cadaveric head specimens, which were injected with colored silicone before microdissection. Another cadaveric head was used for histological section analyses. RESULTS: A lateral or medial location of the abducens nerve dural entrance porus, relative to the midline, was correlated with the course and angulation of the abducens nerve in the petroclival region. The angulation of the abducens nerve was greater and the nerve was closer to the petrous ridge in the lateral type, compared with the medial type. The abducens nerve exhibited three changes in direction, which represented the angulations in the petroclival region, at the dural entrance porus, the petrous apex, and the lateral wall of the internal carotid artery. The abducens nerve was covered by the dural sleeve and the arachnoid membrane, which became attenuated between the second and third angulation points. The abducens nerve was anastomosed with the sympathetic plexus and fixed by connective tissue extensions to the lateral wall of the internal carotid artery and the medial wall of Meckel's cave at the third angulation point. There were two types of trabeculations inside the sinuses around the petroclival region (tough and delicate). CONCLUSION: The petroclival part of the abducens nerve was protected in a dural sleeve accompanied by the arachnoid membrane. Therefore, the risk of abducens nerve injury during petrous apex resection via the anterior transpetrosal approach, with the use of the transvenous route through the inferior petrosal sinus to the cavernous sinus, should be lower than expected. The presence of two anatomic variations in the course of the abducens nerve, in addition to findings regarding nerve angulation and tethering points, may explain the relationships between adjacent structures and the susceptibility to nerve injury with either surgical or endovascular approaches. Venous anatomic variations may account for previously reported cases of subarachnoid hemorrhage with the endovascular approach.

Twenty-five facial arteries were examined radiographically in 19 fresh cadavers that had been injected systemically with a lead oxide-gelatin mixture. Major branches of the facial artery in the upper lip and nose were investigated, and the anatomical variations were classified into three types on the basis of the anatomy of the lateral nasal artery, which was determined as an artery running toward the alar base. In 22 cases (88 percent), the facial artery bifurcated into the lateral nasal artery and superior labial artery at the angle of the mouth. In two cases (8 percent), the facial artery became an angular artery after branching off into the superior labial artery and the lateral nasal artery sequentially. In one case (4 percent), the facial artery became an angular artery after branching off into the superior labial artery, and the lateral nasal artery then branched off from the superior labial artery. Branches from the lateral nasal and superior labial arteries were observed stereographically. Vascular anastomoses between those branches were created in the upper lip, columella base, and nasal tip, and an intimate vascular network was formed. With a vascular network in the mucosa of the upper lip, a bilobed upper-lip flap was created for a clinical case with a full-thickness defect of the ala.

The subdermal plexus was pictured angiographically in five fresh cadavers injected systemically with a lead oxide-gelatin mixture. Subdermal plexus was found either in the subdermal plane or in the deep part of the dermis. Diameters of vessels in the subdermal plexus are not uniform and there are differences in vascular continuity, which means that the subdermal plexus does not always have a random pattern. This observation is important when designing a thin flap.

The drainage pathway of the distally based lesser saphenous-sural veno-neuroadipofascial pedicled fasciocutaneous flap using accompanying arteries of the lesser saphenous vein and sural nerve as nutrient vessels of the flap was radiographically investigated using five fresh cadavers. Small long veins existed along the lesser saphenous vein, and they were considered to be concomitant veins of the accompanying arteries of the lesser saphenous veins. They anastomosed with the lesser saphenous vein in some places and played a role in bypassing valves in the lesser saphenous vein.

The anatomy of the venous system in the pedicles of the radial forearm and anterior tibial reverse flow flaps was investigated in fresh cadavers (n = 6) and their drainage pathways were observed in a radiographic perfusion study of the veins of 2 radial forearm and 2 anterior tibial pedicles. The venous system was found to consist mainly of three types of veins: venae comitantes, communicating veins between the venae comitantes, and vasa vasorum. Valves were identified in all three types of vein. In the venous system, including the vasa vasorum, there was no route of reverse flow that did not pass directly through valves. Valve incompetence was demonstrated in the radiographic perfusion study. However, valve incompetence did not occur in all valves and a difference in valve resistance against reverse flow pressure existed. Veins with relatively weak valve resistance became the drainage pathway. A possible cause of the difference in valve resistance was differences in the anatomy of the valve sinuses.

The purpose of this study was to investigate the artery dilatation performance of the short-duration heating balloon catheter in cadaver stenotic arteries. We designed a prototype short-duration heating balloon catheter that can heat artery media to around 60 °C in 15−25 s by a combination of laser-driven heat generation and continuous fluid irrigation in the balloon. We performed ex vivo short-duration heating dilatation in the cadaver atherosclerotic femoral arteries (initial percent diameter stenosis was 36-98%), with the maximum balloon temperature of 65±5 °C, laser irradiation duration of 25 s, and balloon dilatation pressure of 3.5 atm. The artery lumen configurations before and after the dilatations were assessed with a commercial IVUS system. After the short-duration heating dilatations, the percent diameter stenosis was reduced below 30% without any artery tears or dissections. We estimated that the artery media temperature was raised to around 60 °C in which plaque thickness was below 0.8 mm by a thermal conduction calculation. The estimated maximum temperature in artery adventitia and surrounding tissue was up to 45 °C. We found that the short-duration heating balloon could sufficiently dilate the cadaver stenotic arteries, without thermal injury in artery adventitia and surroundings.

Background: Investigate the effectiveness of beam-hardening (BH) correction using ECG-gated dual-kVp computed tomography (CT) for myocardial imaging. Methods and Results: A human heart specimen and artificial descending aorta were scanned using both dual-kVp and single 120-kVp modes. The myocardial CT values at the anterior and posterobasal walls were 89.4±6.2 and 87.1±6.9HU (P=0.59) for the 69-keV images, and 88.3±5.9 and 49.9±13.5HU (P=0.002) for the 120-kVp images, respectively. Conclusions: Fast-switching dual-kVp technology is feasible for the correction of CT value deficits induced by BH that mimics perfusion defects. (Circ J 2012; 76: 1799–1801)

Sentinel lymph node biopsy (SLNB) has had a great impact on the staging and treatment of cancer. The purpose of this study was to study the lymphatic anatomy of the lower extremities by constructing three-dimensional images using multi-detector-row computed tomography (MDCT). To select appropriate contrast media for MDCT lymphatic imaging in a cadaver, we tested four kinds of contrast media by injecting them into fresh swine kidneys. After the suitable contrast medium was selected, 10 lower extremities from 5 fresh cadavers were studied. After injection of the contrast medium, each lower extremity was scanned with high-spatial-resolution MDCT. The zinc oxide mixture was found to be the most appropriate contrast formula for MDCT imaging of cadaver lymphatics in terms of CT value and no extravasation. The high-resolution MDCT imaging revealed two different superficial lymphatic pathways in the legs. One lymphatic pathway accompanying the great saphenous vein had a constant course and was connected to the superficial inguinal lymph nodes. However, another pathway, along the small saphenous vein, was variable. Some of the deep lymphatic vessels bypassed the inguinal lymph nodes. Using a new protocol, we were able to construct three-dimensional images of the lower extremity lymphatics in a cadaver model. MDCT imaging provided novel information about two different superficial lymphatic pathways in the lower extremities.

In vitro effects of cytokines and therapeutic drugs on antibody dependent cellular cytotoxicity (ADCC) mediated by anticolon antibody were investigated in serum samples from patients with ulcerative colitis. A 51Cr release assay was used to examine ADCC activity with the colon cancer cell line, colo 205, as the target and peripheral blood mononuclear cells as the effector. High ADCC activity was shown in 13 of 32 (41%) patients with ulcerative colitis. This ADCC activity was inhibited by protein A treatment of the serum samples. Interleukin 2 (IL2) activated effector cells could enhance ADCC activity, but interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) had no effect on the cytotoxic activity of effector cells. Treatment of target cells with IFN-gamma increased the vulnerability of these cells to ADCC with a large increase of intercellular adhesion molecule-1 (ICAM-1) expression on their surface. Monoclonal antibodies to ICAM-1 inhibited this IFN-gamma enhanced ADCC activity. Interestingly, prednisolone (PSL) reduced ADCC activity, but sulphasalazine (SASP) or 5-aminosalicylic acid (5-ASA) did not. These results suggest that IL2 and IFN-gamma could enhance colonic epithelial cell injury mediated by the ADCC mechanism in ulcerative colitis and that ADCC enhanced by cytokines is restored by PSL treatment.

Microwave (MW) has the advantage of accelerating infiltration of fixatives into tissue blocks, but the disadvantage of causing the temperature of the fixatives and tissue blocks to rise. We tried to minimize the temperature elevation during MW irradiation by applying ultrasound (US) in combination with MW oven furnishing US generator. US was uneffective in reducing the rise of temperature, however, it was able to enhance the rapid tissue fixation. Electron microscopic examination showed that the fine structure of organs, such as liver, pancreas, submandibular gland, small intestine, and kidney, was well preserved. Characteristically, the matrix of mitochondria appeared electron-dense, and the marginal zone of zymogen granules in the pancreas was more electron-opaque than the core of the granule. The immunoreactivity of zymogen granules to anti-amylase antibody was strong. The deformation or disorder of cell structure due to the thermal effect and cavitation that can be caused by US was not seen. US can be useful for histologic and immunohistochemical study.

The study goals were to demonstrate the superior laryngeal artery in detail with angiograms and to understand its vasculature three-dimensionally. Three fresh cadavers were totally injected with lead oxide-gelatin mixture. The larynx with the surrounding tissue was resected and radiographed stereoscopically with soft X ray system. We get informed consent from a person in question and the bereaved family. The superior laryngeal artery was divided into the ascending and descending branches. The ascending branch supplied the epiglottis chiefly from the ventral surface, and anastomosed with branches of the lingual artery. The descending branch supplied the vestibular and vocal folds, muscles of the larynx and mucosa over the muscles, and anastomosed with distal branches of the superior thyroid artery. Stereographic angiograms and macroscopic observation enabled us to understand vasculature of the superior laryngeal artery.

Amyloid beta (Abeta) has long been implicated in the pathogenesis of Alzheimer's disease (AD). Little is known, however, about the intracellular events in neurons which lead to memory loss related to AD. Focusing on the fact that an AD-specific neuroprotective peptide named humanin (HN) inhibits AD-related neurotoxicity by activating the JAK2/STAT3 signaling axis, we recently found that age- and disease-dependent deterioration in the JAK2/STAT3 axis plays a critical role in the pathogenesis of AD.Here we summarize the neuroprotective effect of HN and its derivative, named colivelin (CLN), and also review the roles of the JAK2/STAT3 axis in memory impairment related to AD.The JAK2/STAT3 axis is a major transducer of HN-mediated neuroprotective activity. Abeta-dependent inactivation of the JAK2/STAT3 axis in hippocampal neurons causes cholinergic dysfunction via pre- and post-synaptic mechanisms, which leads to memory impairment related to AD. This provides not only a novel pathological hallmark of AD but also a novel target in AD therapy.

Previously, we have found that a prior burn insult induces lethal acute lung injury (ALI) and overproduction of proinflammatory cytokines after LPS challenge in mice. The current study was aimed to determine the role of IL-18 in burn-induced LPS hypersensitivity. Except sham group, mice were subjected to a 15% total body surface area full-thickness burn and either untreated or treated with IL-18 alone, IL-18 + anti-IL-10 antibody or IL-18 + isotype immunoglobulin G. LPS was intravenously administered to all mice on the 11th day, and the mice were killed at the indicated time point, or survival was examined. We additionally examined cytokine production by splenic cells in vitro for the elucidation of immunologic mechanisms. Unexpectedly, the liver IL-18 decreased transiently after burn injury, and in vivo IL-18 supplementation improved survival and ameliorated ALI, as well as reducing the lung contents of all cytokines examined, except IL-10. Neutralization of IL-10 cancelled the protective effect of IL-18. In splenic macrophages obtained from burned mice, the production of macrophage inflammatory protein 2 (MIP-2), TNF-alpha, and IL-10 was augmented, whereas in vivo IL-18 supplementation decreased MIP-2 production, but increased IL-10 production. Furthermore, a physiological concentration of IL-18 directly attenuated MIP-2 production by splenic cells in vitro. Burn injury induces LPS hypersensitivity through augmented production of proinflammatory cytokines by systemic macrophages. IL-18 supplementation is protective for LPS-induced lethal ALI through the direct anti-inflammatory effect on macrophages as well as by in vivo acceleration of IL-10 production, and could thus be an effective prophylactic strategy against septic complications in critically ill patients.

The role of tumor necrosis factor alpha (TNF-alpha) in the pathogenesis of autoimmune diabetes mellitus was tested in the nonobese mouse (NOD) model system. The effects of TNF-alpha were assessed on three levels: (i) insulitis development, (ii) development of overt diabetes, (iii) adoptive transfer of diabetes by splenic lymphocytes. Spontaneous diabetes mellitus was blocked in NOD mice by long-term treatment with recombinant TNF-alpha. Treatment with TNF-alpha caused a significant reduction in the lymphocytic infiltration associated with the destruction of the insulin-producing beta cells. Class II major histocompatibility complex Ia expression by islet cells was not up-regulated by TNF-alpha. Moreover, TNF-alpha was able to suppress the induction of diabetes in adoptive transfer of lymphocytes from diabetic female mice to young nondiabetic male NOD mice. These activities of TNF-alpha were shared by interleukin 1 alpha in this system. These studies have implications for the pathogenesis and therapy of autoimmune diabetes mellitus.

Background It is well known that venous drainage of the medial plantar flap is performed by two venous systems: cutaneous veins visible through the skin that drain into the great saphenous vein; and deep veins, namely, accompanying veins of the medial plantar artery. However, there are only a few illustrations of the cutaneous veins of the sole in anatomical textbooks. Further clarification of the cutaneous veins of the sole was considered to be useful information in elevating the medial plantar flap. Methods Whole-body or local injection with contrast medium was performed in 10 fresh cadavers. The skin and subcutaneous tissue were elevated and radiographed with a soft x-ray system. In an embalmed cadaver, macroscopic observation was performed. Results In the sole, an intimate venous network was formed by branches of the great saphenous vein, small saphenous vein, and dorsal venous arch. Vascular arrangement of the venous network was not random but characteristic in each region of the sole. In the medial plantar, vessels were arranged toward the anterior margin of the medial malleolus. Conclusion In planning the medial plantar flap, taking the vascular arrangement into consideration is considered to help the flap to avoid venous congestion and to extend the skin portion.

Humanin (HN) and its derivatives, such as Colivelin (CLN), suppress neuronal death induced by insults related to Alzheimer's disease (AD) by activating STAT3 in vitro. They also ameliorate functional memory impairment of mice induced by anticholinergic drugs or soluble toxic amyloid-beta (Abeta) in vivo when either is directly administered into the cerebral ventricle or intraperitoneally injected. However, the mechanism underlying the in vivo effect remains uncharacterized. In addition, from the standpoint of clinical application, drug delivery methods that are less invasive and specific to the central nervous system (CNS) should be developed. In this study, we show that intranasally (i.n.) administered CLN can be successfully transferred to CNS via the olfactory bulb. Using several behavioral tests, we have demonstrated that i.n. administered CLN ameliorates memory impairment of AD models in a dose-responsive manner. Attenuation of AD-related memory impairment by HN derivatives such as CLN appears to be correlated with an increase in STAT3 phosphorylation levels in the septohippocampal region, suggesting that anti-AD activities of HN derivatives may be mediated by activation of STAT3 in vivo as they are in vitro. We further demonstrate that CLN treatment inhibits an Abeta induced decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the medial septum. Combined with the finding that HN derivatives upregulate mRNA expression of neuronal ChAT and vesicular acetylcholine transporter (VAChT) in vitro, it is assumed that CLN may ameliorate memory impairment of AD models by supporting cholinergic neurotransmission, which is at least partly mediated by STAT3-mediated transcriptional upregulation of ChAT and VAChT.

Humanin (HN), a 24-amino-acid neuroprotective peptide, was originally found in the occipital lobe of an autopsied Alzheimer's disease (AD) patient. HN inhibits neuronal death by binding to its specific receptor on the cell membrane and triggering a Jak2/STAT3 prosurvival pathway. The activation of this pathway may represent a therapeutic approach to AD. HN also exhibits neuroprotective activity against toxicity by familial amyotrophic lateral sclerosis (ALS)-related mutant superoxide dismutase (SOD1). Recent investigations established that AGA-(C8R)-HNG17, a 17-amno-acid derivative of HN, is 10(5) times more potent as a neuroprotective than HN; at 10-picomolar and higher concentrations in vitro it completely suppresses neuronal death. Moreover, a 26-amino-acid peptide colivelin (CL), composed of activity-dependent neurotrophic factor (ADNF) C-terminally fused to AGA-(C8R)-HNG17, provides complete neuroprotection at 100-femtomolar or higher concentrations in vitro. A series of experiments using mouse AD and ALS models further established the efficacy of HN derivatives, including CL, against these diseases in vivo. HN and CL can be viewed as drug candidates for neuronal death suppression therapy in AD or ALS.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease for which there is no sufficiently effective therapy. We have reported in our earlier study that intracerebroventricular (i.c.v.) injection of activity-dependent neurotrophic factor (ADNF) improves motor performance of G93A-SOD1 transgenic mice without significant prolongation in survival. Here, we found that i.c.v. injection of a synthetic hybrid peptide named Colivelin composed of ADNF and AGA-(C8R)HNG17, a potent derivative of Humanin that is a bioactive peptide with anti-Alzheimer's disease activity, dose-dependently improved motor performance and prolonged survival of ALS mice. Histological analysis, performed at the age of 120 days, demonstrated increased motoneuronal survival in spinal cords of Colivelin-treated mice as compared with saline- or ADNF-treated mice, indicating that Colivelin is a promising neurotrophic peptide for treatment of ALS.

Background: The platysma flap has often been used for reconstructions of the head and neck, but the arterial anatomy of the platysma itself has not been clarified. Methods: The anterolateral neck skin in five sides of four fresh cadavers that had been injected systemically with a lead oxide–gelatin mixture was elevated and divided into three layers: the skin with adipofascial tissue over the platysma, the platysma, and the adipofascial tissue under the platysma. Radiographs were taken of each specimen using the soft x-ray system. Results: The anterolateral neck skin was chiefly supplied by branches of the submental, facial, superior thyroid, transverse cervical, and occipital arteries, and it was found that the vasculature of the arterial branches can be classified into three groups. In all of the groups, the arterial branches penetrated the platysma and did not run long in the platysma layer. The platysma was supplied by only small vessels from the arterial branches. Furthermore, there was little connection between the vascular plexus of the platysma and that of the skin layer with adipofascial tissue above the platysma and the platysma located in the subcutaneous tissue. Conclusions: The platysma flap should be considered fasciocutaneous rather than musculocutaneous. Therefore, the platysma flap should usually be elevated with the deep adipofascial tissue under the platysma. Flap survival is threatened if it is elevated without the adipofascial tissue under the muscle as with a usual musculocutaneous flap.

Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron disease, affecting mostly middle-aged people. There are no curative therapies for ALS. Several lines of evidence have supported the notion that the proapoptotic property of familial ALS (FALS)-linked mutant Cu/Zn-superoxide dismutase-1 (SOD1) genes may play an important role in the pathogenesis of some FALS cases. Here we found that activity-dependent neurotrophic factor (ADNF), a neurotrophic factor originally identified to have the anti-Alzheimer's disease (AD) activity, protected against neuronal cell death caused by FALS-linked A4T-, G85R- and G93R-SOD1 in a dose-responsive fashion. Notably, ADNF-mediated complete suppression of SOD1 mutant-induced neuronal cell death occurs at concentrations as low as 100 fM. ADNF maintains the neuroprotective activity even at concentrations of more than 1 nM. This is in clear contrast to the previous finding that ADNF loses its protective activity against neurotoxicity induced by AD-relevant insults, including some familial AD genes and amyloid beta peptide at concentrations of more than 1 nM. Characterization of the neuroprotective activity of ADNF against cell death caused by SOD1 mutants revealed that CaMKIV and certain tyrosine kinases are involved in ADNF-mediated neuroprotection. Moreover, in vivo studies showed that intracerebroventricularly administered ADNF significantly improved motor performance of G93A-SOD1 transgenic mice, a widely used model of FALS, although survival was extended only marginally. Thus, the neuroprotective activity of ADNF provides a novel insight into the development of curative drugs for ALS.

Arterial and venous anatomy and their relation to the anterolateral thigh flap were examined in 10 specimens of six fresh cadavers in which radiopaque materials were injected into both the arterial and venous systems. Territories and positions of individual perforating arteries were measured, and the venous drainage pathway of the flap was analyzed. All specimens were radiographed stereoscopically to observe the three-dimensional structure of the arteries and veins. The territory of each perforating artery was smaller than expected. Most of the venous blood that had perfused the dermis was considered to pool in a polygonal venous network located in the skin layer and to enter the descending branch of the lateral circumflex femoral artery through large descending veins. The venous territories were considered different from the arterial territories. The findings in this study suggest that the design of the anterolateral thigh flap should be based on the venous architecture rather than on the arterial architecture and that the flap survival rate might be improved if thinning is performed appropriately.

Pulmonary fibrosis is caused by various known and unknown aetiologies, but the key pathogenic mechanisms are still ill-defined. Chemokines are a large family of chemotactic cytokines that play pivotal roles in various inflammatory diseases. In the present study, the roles of chemokines in a rat model of radiation pneumonitis/ pulmonary fibrosis were examined. Accumulation of inflammatory cells and pneumonitis were observed on day 28, and diffuse alveolar wall thickening with extensive fibrosis was observed on day 56. In addition to the previously reported CCL2 (macrophage chemoattractant protein-1) induction, selective upregulation of CCL22 (macrophage-derived chemokine) and CCL17 (thymus and activation-regulated chemokine) were demonstrated for the first time in the irradiated lung tissues. Immunohistochemically, it was demonstrated that CCL22 and CCL17 were localised primarily to alveolar macrophages, whereas their receptor CC chemokine receptor 4 (CCR4) was detected on alveolar lymphocytes and macrophages. On further analysis of bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis and sarcoidosis, elevated levels of CCL22, but not of CCL17, were observed in the idiopathic pulmonary fibrosis patients. Since these two chemokines play pivotal roles in various type-2 T-helper cell-dominant diseases, it was speculated that CCL22, and probably CCL17, are involved in the pathophysiology of radiation pneumonitis/pulmonary fibrosis and idiopathic pulmonary fibrosis through the recruitment of CC chemokine receptor 4-positive type-2 T-helper cells and alveolar macrophages.

The arterial anatomy of the lower lip was investigated in 12 sides of six fresh cadavers that had been injected systemically with a lead oxide and gelatin mixture. We found that the blood supply of the lower lip was derived from the facial artery and three dominant labial arteries: the inferior labial artery, the horizontal labiomental artery, and the vertical labiomental artery. The inferior labial artery was derived from the facial artery or superior labial artery, and ran through the submucous tissue horizontally. The horizontal labiomental artery arising from the facial artery was located between the depressor labii inferioris muscle and orbicularis oris muscle. The vertical labiomental artery arose from the submental artery. These three arteries provided small vessels that traversed vertically. These small vessels and the small branches of the facial artery, that run superficial and deep to the orbicularis oris muscle, formed a vascular network in subcutaneous and submucous tissues and minute vessels branched off to the skin, mucosa, and muscles.

The arterial anatomical features of the upper palpebra were examined in both sides of seven fresh cadavers that had been systemically injected with a lead oxide/gelatin mixture. All specimens were stereoscopically radiographed for analysis of the three-dimensional structure of the arteries and were macroscopically dissected for observation of the relationships between the arteries and the other tissues. Cross-sections were prepared from one specimen and examined histologically. In all cases, there were four arterial arcades in the upper palpebra, namely, the marginal, peripheral, superficial orbital, and deep orbital arcades. Each arcade provided small vertical branches. The vertical branches coursed on both sides of the orbicularis oculi muscle and on both sides of the tarsal plate. From these small vertical branches, fine vessels branched off to the skin, muscle, and tarsal plate. These findings are important for avoiding complications such as bleeding and are useful for designing local flaps, such as switch flaps, for reconstructive surgical procedures.