Dosimetric comparison of absolute and relative dose distributions between tissue maximum ratio and convolution algorithms for acoustic neurinoma plans in Gamma Knife radiosurgery

Background

The treatment planning for Gamma Knife (GK) stereotactic radiosurgery (SRS) that performs dose calculations based on tissue maximum ratio (TMR) algorithm has disadvantages in predicting dose in tissue heterogeneity. The latest version of the planning software is equipped with a convolution dose algorithm as an optional extra and the new algorithm is able to compensate for head inhomogeneity. However, the effect of this improved calculation method requires detailed validation in clinical cases. In this study, we compared absolute and relative dose distributions of treatment plans for acoustic neurinoma between TMR and the convolution calculation.

Methods

Twenty-nine clinically used plans created by TMR algorithm were recalculated by convolution method. Differences between TMR and convolution were evaluated in terms of absolute dose (beam-on time), dosimetric parameters including target coverage, selectivity, conformity index, gradient index, radical homogeneity index and the dose-volume relationship.

Results

The discrepancy in estimated absolute dose to the target ranged from 1 to 7 % between TMR and convolution. In addition, dosimetric parameters of the two methods achieved statistical significance. However, it was difficult to see the change of relative dose distribution by visual assessment on a monitor.

Conclusions

Convolution, heterogeneity correction calculation, and the algorithm are necessary to reduce the dosimetric uncertainty of each case in GK SRS.     

Cell transplantation therapy for a rat model of secondary lymphedema

Background

Although lymphedema is a progressive and lifelong condition, substantial advances in therapeutic intervention are limited. The development of a novel therapy for lymphedema is urgent for those patients suffering from it. The aim of this study was to investigate the usefulness of a new cell transplantation therapy in the rat tail model of secondary lymphedema.

Materials and methods

We prepared two cell sources, human dermal microvascular endothelial cells (HDMECs) and lymphatic endothelial cells (LECs), which were collected from the resected normal dermis of patients with breast cancer. After the animal model of secondary lymphedema of the nude rats' tails was established, phosphate-buffered saline, purified LECs, or unpurified HDMECs were injected in the rats' tails five times for more than 14 d. The evaluations were performed by measuring the circumference, fluorescence lymphography, and histologic analysis of the rats' tails between each group.

Results

The isolated cells by the simple immunomagnetic sorting from HDMECs were positive for a pan-endothelial marker (CD31) and lymphatic-specific markers (podoplanin, lymphatic vessel endothelial hyaluronan receptor-1 [LYVE-1], and prospero homebox 1 [Prox-1]), and were considered to be LECs. In the cell transplantation group, which was injected with human LECs, the circumference, lymphatic flow, and thickness of the skin of the rat tail became thinner than the groups injected with unpurified HDMECs or phosphate-buffered saline. Immunohistochemistry of the rat tails showed that the number of own lymphatic vessels was increased in the purified LEC transplantation group compared with the other groups. Furthermore, in the LEC transplantation group, some vessels were immunopositive for human-podoplanin or -LYVE-1 and the areas adjacent to the vessels were rat-podoplanin or -LYVE-1 immunopositive.

Conclusions

Our findings indicate that cell transplantation therapy using human LECs improved the secondary lymphedema in the nude rat tail. This therapeutic strategy may merit clinical investigation in patients with lymphedema.     

Food rewards modulate the activity of song neurons in Bengalese finches

Vocal learning, a critical component of speech acquisition, is a rare trait in animals. Songbirds are a well‐established animal model in vocal learning research; male birds acquire novel vocal patterns and have a well‐developed ‘song system’ in the brain. Although this system is unique to songbirds, anatomical and physiological studies have reported similarities between the song system and the thalamo‐cortico‐basal ganglia circuit that is conserved among reptiles, birds, and mammals. Here, we focused on the similarity of the neural response between these two systems while animals were engaging in operant tasks. Neurons in the basal ganglia of vertebrates are activated in response to food rewards and reward predictions in behavioral tasks. A striatal nucleus in the avian song system, Area X, is necessary for vocal learning and is considered specialized for singing. We found that the spiking activity of singing‐related Area X neurons was modulated by food rewards and reward signals in an operant task. As previous studies showed that Area X is not critical for general cognitive tasks, the role of Area X in general learning might be limited and vestigial. However, our results provide a new viewpoint to investigate the independence of the vocal learning system from neural systems involved in other cognitive tasks.     

Endoscopic ultrasound with double-balloon endoscopy in the evaluation of small-bowel disease

Background

Double-balloon endoscopy (DBE) has become a new standard in enteroscopy. However, it may be difficult to make a diagnosis or plan treatment strategy with endoscopic visualization alone. The addition of endoscopic ultrasonography (EUS) has the potential to improve the ability to establish the diagnosis and develop a treatment strategy. The present study was conducted to assess the feasibility and usefulness of EUS with DBE.

Methods

EUS with DBE was performed in 31 of 891 patients who underwent DBE from July 2004 to March 2011 at Jichi Medical University Hospital. We analyzed the EUS findings for lesions and evaluated the usefulness of EUS considering the following three factors: qualitative diagnostic value for lesions, depth grading of lesions, and evaluation of the structure of severe strictures prior to endoscopic balloon dilation.

Results

EUS was performed for 31/32 lesions (97 %) in 31 patients. EUS findings were informative for 29/32 lesions (91 %). EUS findings were useful for establishing a qualitative diagnosis in 15/25 lesions (60 %). EUS findings for depth grading provided useful information for determining the therapeutic strategy in 11/13 lesions (85 %). EUS with DBE was useful in the evaluation of strictures for all six lesions (100 %). The overall usefulness of EUS with DBE on decision making was 72 % (23/32) in this study.

Conclusions

EUS with DBE is feasible and useful. It provides additional information on small-bowel disease and contributes to establishing a precise diagnosis and selection of an appropriate therapeutic strategy.     

Validation of accuracy in image co-registration with computed tomography and magnetic resonance imaging in Gamma Knife radiosurgery

The latest version of Leksell GammaPlan (LGP) is equipped with Digital Imaging and Communication in Medicine (DICOM) image-processing functions including image co-registration. Diagnostic magnetic resonance imaging (MRI) taken prior to Gamma Knife treatment is available for virtual treatment pre-planning. On the treatment day, actual dose planning is completed on stereotactic MRI or computed tomography (CT) (with a frame) after co-registration with the diagnostic MRI and in association with the virtual dose distributions. This study assesses the accuracy of image co-registration in a phantom study and evaluates its usefulness in clinical cases. Images of three kinds of phantoms and 11 patients are evaluated. In the phantom study, co-registration errors of the 3D coordinates were measured in overall stereotactic space and compared between stereotactic CT and diagnostic CT, stereotactic MRI and diagnostic MRI, stereotactic CT and diagnostic MRI, and stereotactic MRI and diagnostic MRI co-registered with stereotactic CT. In the clinical study, target contours were compared between stereotactic MRI and diagnostic MRI co-registered with stereotactic CT. The mean errors of coordinates between images were < 1 mm in all measurement areas in both the phantom and clinical patient studies. The co-registration function implemented in LGP has sufficient geometrical accuracy to assure appropriate dose planning in clinical use.     

Stretching versus transitory icing: which is the more effective treatment for attenuating muscle fatigue after repeated manual labor?

Purpose

Effective recovery from muscle fatigue, especially during rest intervals between periods of high-intensity activity, is important to ensure optimal subsequent performance. Stretching and icing are two types of treatment used for muscle recovery in such situations. However, their effectiveness remains unclear because of a lack of adequate evidence and/or discrepant results of previous studies. We performed a study to elucidate the effects of stretching and icing on muscle fatigue in subjects performing alternating muscle contraction and rest.

Methods

Sixteen healthy male subjects aged 21–27 years were evaluated. Each subject performed repeated isometric muscle contraction exercises that involved lifting and holding a dumbbell to induce muscle fatigue. Four treatments were performed during the rest periods between isometric muscle contraction: static stretching, ballistic stretching, no stretching, or icing. Electromyography and relative muscle oxygen saturation measurements were performed during the exercises. Muscle fatigue was indirectly estimated by the decline in the median frequency of the electromyographic signal.

Results

Stretching between alternate isometric muscle contraction exercises resulted in a significantly lower median frequency of the electromyographic signal than did no stretching. There was no significant difference in the change in the median frequency between static and ballistic stretching. Conversely, icing between alternate exercises did not decrease the median frequency.

Conclusions

Stretching, whether static or ballistic, is not beneficial for recovery from muscle fatigue and may actually inhibit recovery. Icing may more effectively induce such recovery and thus may be a better choice between the two treatment techniques.     

Basophilic stippling in red blood cells in the bone marrow: indication for lead poisoning diagnosis

A 40-year-old man presented at our hospital with anaemia that had been undiagnosed for 2 years. Blood tests, endoscopy, and contrast-enhanced computed tomography were performed, but a definitive diagnosis could not be made. A subsequent bone marrow biopsy revealed basophilic stippling in transformed red blood cells, which led to a differential diagnosis of lead poisoning. Additional tests revealed elevated levels of lead in the blood. Basophilic stippling is generally found on a peripheral blood smear in lead poisoning patients; however, in this case, basophilic stippling was found only on the bone marrow smear and not in the blood smear. Even if basophilic stippling is not found in the peripheral blood, lead poisoning cannot be excluded.     

Longitudinal Analysis of Neutralizing Potency against SARS-CoV-2 in the Recovered Patients after Treatment with or without Favipiravir

The effect of treatment with favipiravir, an antiviral purine nucleoside analog, for coronavirus disease 2019 (COVID-19) on the production and duration of neutralizing antibodies for SARS-CoV-2 was explored. There were 17 age-, gender-, and body mass index-matched pairs of favipiravir treated versus control selected from a total of 99 patients recovered from moderate COVID-19. These subjects participated in the longitudinal (>6 months) analysis of (i) SARS-CoV-2 spike protein’s receptor-binding domain IgG, (ii) virus neutralization assay using authentic virus, and (iii) neutralization potency against original (WT) SARS-CoV-2 and cross-neutralization against B.1.351 (beta) variant carrying triple mutations of K417N, E484K, and N501Y. The results demonstrate that the use of favipiravir: (1) significantly accelerated the elimination of SARS-CoV-2 in the case vs. control groups (p = 0.027), (2) preserved the generation and persistence of neutralizing antibodies in the host, and (3) did not interfere the maturation of neutralizing potency of anti-SARS-CoV-2 and neutralizing breadth against SARS-CoV-2 variants. In conclusion, treatment of COVID-19 with favipiravir accelerates viral clearance and does not interfere the generation or maturation of neutralizing potency against both WT SARS-CoV-2 and its variants.