Views of Specialist Clinicians and People With Multiple Sclerosis on Upper Limb Impairment and the Potential Role of Virtual Reality in the Rehabilitation of the Upper Limb in Multiple Sclerosis: Focus Group Study.

BACKGROUND: Finding enjoyable and effective long-term approaches to rehabilitation for improving the upper limb (UL) function of people with multiple sclerosis (MS) is challenging. Using virtual reality (VR) could be a solution to this challenge; however, there is a lack of reporting on the views of people with MS and clinicians on VR-based approaches and recommendations for games for rehabilitation. OBJECTIVE: This study aims to identify common UL problems and their related current therapeutic approaches for people with MS, and to explore the opinions of people with MS and specialist clinicians on VR and obtain suggestions for the development and design of VR games. METHODS: Separate focus groups were conducted with people with MS, recruited through the MS Society UK's research network, and clinicians, recruited through the MS Trust Therapists in MS network. A total of 10 people with MS (2 focus groups) and 8 clinicians (5 physiotherapists, 2 occupational therapists, and 1 MS nurse in 2 focus groups) were involved. The focus groups were recorded and transcriptions were analyzed using theme-based content analysis. RESULTS: People with MS commonly reported that their UL problems interfered with activities of daily living and resulted in the loss of meaningful hobbies such as writing. Many people with MS neglected UL exercise and found strategies for adapting to the UL impairments. Similarly, clinicians stated UL rehabilitation was neglected within their service and that it was challenging to find interesting treatment strategies. VR was suggested by both participant groups as a solution, as it was convenient for people with MS to access and it could provide a more engaging and disguised approach to exercise. There were shared concerns with cybersickness and disengagement with using VR approaches. Both groups agreed games should be meaningful and adaptable for users but suggested different VR activities, with clinicians suggesting games directly reflecting activities of daily living and people with MS suggesting more abstract activities. CONCLUSIONS: VR was well received by both people with MS and clinicians for UL rehabilitation. Recommendations were made for the development of VR rehabilitation games which are personalized and customizable for the varying abilities of people with MS.

Intensity-modulated radiotherapy and chemotherapy for canine right atrial tumors: A retrospective study of seven dogs.

Most primary cardiac tumors in dogs are located in the right atrium/atrial appendage, with hemangiosarcoma being the most common. The aims of this retrospective, case series were to describe outcomes for seven dogs with right atrial tumors treated with hypofractionated intensity-modulated radiotherapy and concurrent vinblastine and propranolol. One dog had a complete response, four dogs had partial responses and two dogs had stable disease after treatment. Effusions resolved in all dogs. Median progression-free survival was 290 days. Five dogs died from metastatic disease, one dog from unrelated neoplasia, and one dog is alive. Median overall survival was 326 days. Three dogs with confirmed hemangiosarcoma survived 244, 326, and 445 days. Two dogs developed clinically significant, but nonfatal, cardiac arrhythmias. One dog that received three courses of radiation had subclinical myocardial and arterial fibrosis at necropsy. Hypofractionated chemoradiotherapy was well tolerated and may provide clinical benefit in dogs with right atrial tumors.

Helical TomoTherapy Total Lymphoid Irradiation and Hematopoietic Cell Transplantation for Kidney Transplant Tolerance in Rhesus Macaques.

Development of a post-transplant kidney transplant tolerance induction protocol involving a novel total lymphoid irradiation (TLI) conditioning method in a rhesus macaque model is described. We examined the feasibility of acheiving tolerance to MHC 1-haplotype matched kidney transplants by establishing a mixed chimeric state with infusion of donor hematopoietic cells (HC) using TomoTherapy TLI. The chimeric state was hypothesized to permit the elimination of all immunosuppressive (IS) medications while preserving allograft function long-term without development of graft-versus-host-disease (GVHD) or rejection. An experimental group of 11 renal transplant recipients received the tolerance induction protocol and outcomes were compared to a control group (n = 7) that received the same conditioning but without donor HC infusion. Development of mixed chimerism and operational tolerance was accomplished in two recipients in the experimental group. Both recipients were withdrawn from all IS and continued to maintain normal renal allograft function for 4 years without rejection or GVHD. None of the animals in the control group achieved tolerance when IS was eliminated. This novel experimental model demonstrated the feasibility for inducing of long-term operational tolerance when mixed chimerism is achieved using a TLI post-transplant conditioning protocol in 1-haplotype matched non-human primate recipients of combined kidney and HC transplantation.

Tomotherapy Applied Total Lymphoid Irradiation and Allogeneic Hematopoietic Cell Transplantation Generates Mixed Chimerism in the Rhesus Macaque Model.

Development of a new methodology to induce immunological chimerism after allogeneic hematopoietic cell (HC) transplantation in a rhesus macaque model is described. The chimeric state was achieved using a non-myeloablative, helical tomotherapy-based total lymphoid irradiation (TomoTLI) conditioning regimen followed by donor HC infusions between 1-haplotype matched donor/recipient pairs. The technique was tested as a feasibility study in an experimental group of seven rhesus macaques that received the novel TomoTLI tolerance protocol and HC allo-transplants. Two tomotherapy protocols were compared: TomoTLI (n = 5) and TomoTLI/total-body irradiation (TBI) (n = 2). Five of seven animals developed mixed chimerism. Three of five animals given the TomoTLI protocol generated transient mixed chimerism with no graft-versus-host disease (GVHD) with survival of 33, 152 and >180 days. However, the inclusion of belatacept in addition to a single fraction of TBI resulted in total chimerism and fatal GVHD in both animals, indicating an unacceptable conditioning regimen.

Definitive-intent intensity modulated radiotherapy for modified-Adams' stage 4 canine sinonasal cancer: A retrospective study of 29 cases (2011-2017).

Dogs with sinonasal tumors with cribriform plate lysis (modified Adams' stage 4) treated with non-conformal definitive radiotherapy (RT) have short median survivals of 6-7 months. Intensity-modulated radiotherapy with its greater conformality and tumor dose homogeneity may result in more favorable outcomes. Dogs with epithelial or mesenchymal sinonasal tumors and CT evidence of cribriform lysis that received 10 daily fractions of 4.2 Gray using IMRT by helical tomotherapy were included in this single-institution retrospective case series study. Dogs with distant metastasis, previous treatment, or concurrent chemotherapy were excluded. Based on CT, tumors were divided into two groups: cribriform plate lysis only (stage 4a) or intracranial extension (stage 4b). Twenty-nine dogs were included, 23 with carcinoma and six with sarcoma. Eight dogs had stage 4b tumors; two presented with neurologic signs. Two dogs had lymph node metastasis at diagnosis, one confirmed and one suspected. Radiation dose distributions were standardized and patient positioning for RT was verified daily using on-board megavoltage CT. All evaluable dogs had improvement of clinical signs. Median progression free survival was 177 days (95% CI, 128-294 days). Median overall survival was 319 days (95% CI, 188-499 days). Radiotherapy was well tolerated. The most common side effect was grade 1 or 2 oral mucositis. Two dogs that received additional treatment at progression (stereotactic RT [1]; surgery [1]) developed significant late effects. Image-guided definitive-intent IMRT may improve survival in dogs with modified Adams' stage 4 sinonasal tumors and is associated with low morbidity. Intracranial tumor extension was not prognostic in this cohort of uniformly treated dogs.

Volumetric tumor response assessment is inefficient without overt clinical benefit compared to conventional, manual veterinary response assessment in canine nasal tumors.

Accurate assessment of tumor response to therapy is critical in guiding management of veterinary oncology patients and is most commonly performed using response evaluation criteria in solid tumors criteria. This process can be time consuming and have high intra- and interobserver variability. The primary aim of this serial measurements, secondary analysis study was to compare manual linear tumor response assessment to semi-automated, contoured response assessment in canine nasal tumors. The secondary objective was to determine if tumor measurements or clinical characteristics, such as stage, would correlate to progression-free interval. Three investigators evaluated paired CT scans of skulls of 22 dogs with nasal tumors obtained prior to and following radiation therapy. The automatically generated tumor volumes were not useful for canine nasal tumors in this study, characterized by poor intraobserver agreement between automatically generated contours and hand-adjusted contours. The radiologist's manual linear method of determining response evaluation criteria in solid tumors categorization and tumor volume is significantly faster (P < .0001) but significantly underestimates nasal tumor volume (P < .05) when compared to a contour-based method. Interobserver agreement was greater for volume determination using the contour-based method when compared to response evaluation criteria in solid tumors categorization utilizing the same method. However, response evaluation criteria in solid tumors categorization and percentage volume change were strongly correlated, providing validity to response evaluation criteria in solid tumors as a rapid method of tumor response assessment for canine nasal tumors. No clinical characteristics or tumor measurements were significantly associated with progression-free interval.

Short survival time following palliative-intent hypofractionated radiotherapy for non-resectable canine thyroid carcinoma: A retrospective analysis of 20 dogs.

Radiotherapy is the treatment of choice for non-resectable canine thyroid carcinoma. High tumor response rates and median survival times of 2 years or longer have been previously reported with conventionally fractionated and hypofractionated protocols, even in dogs with distant metastasis. The objective of this retrospective, descriptive, case series study was to evaluate the clinical outcomes of dogs with thyroid carcinoma irradiated with palliative intent using hypofractionated radiotherapy at our institution. Medical records of 20 dogs treated between 1999 and 2014 were reviewed. All dogs had macroscopic primary tumors and presented with tumor-related clinical signs. Median longest tumor diameter was 10 cm. Nineteen dogs (95%) had metastasis (7/19 lymph node; 16/19 distant metastasis). Most dogs were treated with four weekly fractions of 6.5-8 Gy. Radiotherapy was well tolerated in 17 dogs; three died of respiratory compromise before completing radiotherapy. Eleven dogs received adjuvant chemotherapy. Five dogs experienced a local tumor response including two complete and three partial responses. Overall median survival time was 170 days (range, 1-824 days; 95% CI: 58-392 days). Of potential variables examined (radiation delivery system and protocol, tumor size and location, vascular/lymphatic invasion, metastatic disease, chemotherapy, tumor response), only achievement of complete or partial response was predictive of overall survival. In contrast to previously reported cohorts, dogs with clinical signs and stage IV disease predominated in this study. Previous studies may over-estimate survival following hypofractionated radiotherapy in dogs with advanced thyroid carcinoma.

SINGLE INSTITUTION VARIABILITY IN INTENSITY MODULATED RADIATION TARGET DELINEATION FOR CANINE NASAL NEOPLASIA.

Contouring variability is a significant barrier to the accurate delivery and reporting of radiation therapy. The aim of this descriptive study was to determine the variation in contouring radiation targets and organs at risk by participants within our institution. Further, we also aimed to determine if all individuals contoured the same normal tissues. Two canine nasal tumor datasets were selected and contoured by two ACVR-certified radiation oncologists and two radiation oncology residents from the same institution. Eight structures were consistently contoured including the right and left eye, the right and left lens, brain, the gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). Spinal cord, hard and soft palate, and bulla were contoured on 50% of datasets. Variation in contouring occurred in both targets and normal tissues at risk and was particularly significant for the GTV, CTV, and PTV. The mean metric score and dice similarity coefficient were below the threshold criteria in 37.5-50% and 12.5-50% of structures, respectively, quantitatively indicating contouring variation. This study refutes our hypothesis that minimal variation in target and normal tissue delineation occurs. The variation in contouring may contribute to different tumor response and toxicity for any given patient. Our results also highlight the difficulty associated with replication of published radiation protocols or treatments, as even with replete contouring description the outcome of treatment is still fundamentally influenced by the individual contouring the patient.

Image-guided stereotactic radiotherapy in 4 dogs with intracranial neoplasia.

The purpose of this study was to describe the use, and side effects, of a novel stereotactic radiotherapy protocol using TomoTherapy(®) in 4 dogs with confirmed or suspected primary extra-axial intracranial neoplasia. Three fractions of 8 Gy were prescribed. Acute side effects were noted in 1 dog; no late effects were noted.

Radiothérapie stéréotactique guidée par imagerie chez 4 chiens atteints de néoplasie intracrâniale. Cette étude avait pour objectif de décrire l'utilisation et les effets secondaires d'un nouveau protocole de radiothérapie stéréotactique utilisant la TomoTherapyMD chez 4 chiens atteints de néoplasie intracrâniale extra-axiale primaire confirmée ou suspectée. Trois fractions de 8 Gy ont été prescrites. Des effets secondaires aigus ont été observés chez 1 chien; aucun effet tardif n'a été observé.(Traduit par Isabelle Vallières).

Computed Tomography Imaging in Oncology.

Computed tomography (CT) imaging has become the mainstay of oncology, providing accurate tumor staging and follow-up imaging to monitor treatment response. Presurgical evaluation of tumors is becoming commonplace and guides surgeons as to the extent and whether complete tumor resection is possible. CT imaging plays a crucial role in radiotherapy treatment planning. CT imaging in oncology has become ubiquitous in veterinary medicine because of increased availability of this imaging modality. This article focuses on CT cancer staging in veterinary oncology, CT imaging for surgical planning, and advances in CT simulation for radiation therapy planning.

INVITED REVIEW--IMAGE REGISTRATION IN VETERINARY RADIATION ONCOLOGY: INDICATIONS, IMPLICATIONS, AND FUTURE ADVANCES.

The field of veterinary radiation therapy (RT) has gained substantial momentum in recent decades with significant advances in conformal treatment planning, image-guided radiation therapy (IGRT), and intensity-modulated (IMRT) techniques. At the root of these advancements lie improvements in tumor imaging, image alignment (registration), target volume delineation, and identification of critical structures. Image registration has been widely used to combine information from multimodality images such as computerized tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) to improve the accuracy of radiation delivery and reliably identify tumor-bearing areas. Many different techniques have been applied in image registration. This review provides an overview of medical image registration in RT and its applications in veterinary oncology. A summary of the most commonly used approaches in human and veterinary medicine is presented along with their current use in IGRT and adaptive radiation therapy (ART). It is important to realize that registration does not guarantee that target volumes, such as the gross tumor volume (GTV), are correctly identified on the image being registered, as limitations unique to registration algorithms exist. Research involving novel registration frameworks for automatic segmentation of tumor volumes is ongoing and comparative oncology programs offer a unique opportunity to test the efficacy of proposed algorithms.

Characterization of a 0.35T MR system for phantom image quality stability and in vivo assessment of motion quantification.

ViewRay is a novel MR-guided radiotherapy system capable of imaging in near real-time at four frames per second during treatment using 0.35T field strength. It allows for improved gating techniques and adaptive radiotherapy. Three cobalt-60 sources (~ 15,000 Curies) permit multiple-beam, intensity-modulated radiation therapy. The primary aim of this study is to assess the imaging stability, accuracy, and automatic segmentation algorithm capability to track motion in simulated and in vivo targets. Magnetic resonance imaging (MRI) characteristics of the system were assessed using the American College of Radiology (ACR)-recommended phantom and accreditation protocol. Images of the ACR phantom were acquired using a head coil following the ACR scanning instructions. ACR recommended T1- and T2-weighted sequences were evaluated. Nine measurements were performed over a period of seven months, on just over a monthly basis, to establish consistency. A silicon dielectric gel target was attached to the motor via a rod. 40 mm total amplitude was used with cycles of 3 to 9 s in length in a sinusoidal trajectory. Trajectories of six moving clinical targets in four canine patients were quantified and tracked. ACR phantom images were analyzed, and the results were compared with the ACR acceptance levels. Measured slice thickness accuracies were within the acceptance limits. In the 0.35 T system, the image intensity uniformity was also within the ACR acceptance limit. Over the range of cycle lengths, representing a wide range of breathing rates in patients imaged at four frames/s, excellent agreement was observed between the expected and measured target trajectories. In vivo canine targets, including the gross target volume (GTV), as well as other abdominal soft tissue structures, were visualized with inherent MR contrast, allowing for preliminary results of target tracking.

Predicting location of recurrence using FDG, FLT, and Cu-ATSM PET in canine sinonasal tumors treated with radiotherapy.

Dose painting relies on the ability of functional imaging to identify resistant tumor subvolumes to be targeted for additional boosting. This work assessed the ability of FDG, FLT, and Cu-ATSM PET imaging to predict the locations of residual FDG PET in canine tumors following radiotherapy. Nineteen canines with spontaneous sinonasal tumors underwent PET/CT imaging with radiotracers FDG, FLT, and Cu-ATSM prior to hypofractionated radiotherapy. Therapy consisted of 10 fractions of 4.2 Gy to the sinonasal cavity with or without an integrated boost of 0.8 Gy to the GTV. Patients had an additional FLT PET/CT scan after fraction 2, a Cu-ATSM PET/CT scan after fraction 3, and follow-up FDG PET/CT scans after radiotherapy. Following image registration, simple and multiple linear and logistic voxel regressions were performed to assess how well pre- and mid-treatment PET imaging predicted post-treatment FDG uptake. R(2) and pseudo R(2) were used to assess the goodness of fits. For simple linear regression models, regression coefficients for all pre- and mid-treatment PET images were significantly positive across the population (P < 0.05). However, there was large variability among patients in goodness of fits: R(2) ranged from 0.00 to 0.85, with a median of 0.12. Results for logistic regression models were similar. Multiple linear regression models resulted in better fits (median R(2) = 0.31), but there was still large variability between patients in R(2). The R(2) from regression models for different predictor variables were highly correlated across patients (R ≈ 0.8), indicating tumors that were poorly predicted with one tracer were also poorly predicted by other tracers. In conclusion, the high inter-patient variability in goodness of fits indicates that PET was able to predict locations of residual tumor in some patients, but not others. This suggests not all patients would be good candidates for dose painting based on a single biological target.

Molecular imaging biomarkers of resistance to radiation therapy for spontaneous nasal tumors in canines.

PURPOSE: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. METHODS AND MATERIALS: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV(max); SUV(mean)) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R(2). RESULTS: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV(mean) (P=.018), and midtreatment FLT SUV(max) (P=.006). Large decreases in FLT SUV(mean) from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV(max) (P=.022) in combination with large FLT response from pretreatment to midtreatment (P=.041). CONCLUSIONS: In addition to tumor volume, pronounced tumor proliferative response quantified using FLT PET, especially when associated with high residual FLT PET at midtreatment, is a negative prognostic biomarker of outcome in canine tumors following radiation therapy. Neither FDG PET nor Cu-ATSM PET were predictive of outcome.

Reproducibility and feasibility of acoustoelastography in the superficial digital flexor tendons of clinically normal horses.

OBJECTIVE: To evaluate the feasibility and repeatability of in vivo measurement of stiffness gradients by means of acoustoelastography in the superficial digital flexor tendons (SDFTs) of clinically normal horses. ANIMALS: 15 clinically normal horses. PROCEDURES: For each horse, stiffness gradient index and dispersion values for SDFTs in both forelimbs were evaluated in longitudinal orientation by use of acoustoelastography at 3 sites (5, 10, and 15 cm distal to the accessory carpal bone) by 2 observers; for each observer, data were acquired twice per site. The left forelimb was always scanned before the right forelimb. Lifting of the contralateral forelimb with the carpus flexed during image acquisition resulted in the required SDFT deformation in the evaluated limb. Interobserver repeatability, intraobserver repeatability, and right-to-left limb symmetry for stiffness gradient index and dispersion values were evaluated. RESULTS: Stiffness gradient index and dispersion values for SDFTs at different locations as well as effects of age or sex did not differ significantly among the 15 horses. Interclass correlation coefficients for interobserver repeatability, intraobserver repeatability, and limb symmetry revealed good to excellent agreement (intraclass correlation coefficients, > 0.74). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that acoustoelastography is a feasible and repeatable technique for measuring stiffness gradients in SDFTs in clinically normal horses, and could potentially be used to compare healthy and diseased tendon states.

Spatiotemporal stability of Cu-ATSM and FLT positron emission tomography distributions during radiation therapy.

PURPOSE: In dose painting, in which functional imaging is used to define biological targets for radiation therapy dose escalation, changes in spatial distributions of biological properties during treatment can compromise the quality of therapy. The goal of this study was to assess the spatiotemporal stability of 2 potential dose painting targets--hypoxia and proliferation--in canine tumors during radiation therapy. METHODS AND MATERIALS: Twenty-two canine patients with sinonasal tumors (14 carcinoma and 8 sarcoma) were imaged before hypofractionated radiation therapy with copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) positron emission tomography/computed tomography (PET/CT) for hypoxia and 3'-deoxy-3'-(18)F-fluorothymidine (FLT) PET/CT for proliferation. The FLT scans were repeated after 2 fractions and the Cu-ATSM scans after 3 fractions. Midtreatment PET/CT images were deformably registered to pretreatment PET/CT images. Voxel-based Spearman correlation coefficients quantified the spatial stability of Cu-ATSM and FLT uptake distributions between pretreatment and midtreatment scans. Paired t tests determined significant differences between the patients' respective Cu-ATSM and FLT correlations coefficients. Standardized uptake value measures were also compared between pretreatment and midtreatment scans by use of paired t tests. RESULTS: Spatial distributions of Cu-ATSM and FLT uptake were stable through midtreatment for both sarcomas and carcinomas: the population mean ± standard deviation in Spearman correlation coefficient was 0.88 ± 0.07 for Cu-ATSM and 0.79 ± 0.13 for FLT. The patients' Cu-ATSM correlation coefficients were significantly higher than their respective FLT correlation coefficients (P=.001). Changes in Cu-ATSM SUV measures from pretreatment to midtreatment were histology dependent: carcinomas experienced significant decreases in Cu-ATSM uptake (P<.05), whereas sarcomas did not (P>.20). Both histologies experienced significant decreases in FLT uptake (P<.05). CONCLUSIONS: Spatial distributions of Cu-ATSM were very stable after a few fractions of radiation therapy. FLT spatial distributions were generally stable early in therapy, although they were significantly less stable than Cu-ATSM distributions. Canine tumors had significantly lower proliferative activity at midtreatment than at pretreatment, and they experienced histology-dependent changes in Cu-ATSM uptake.

Heterogeneity in intratumor correlations of 18F-FDG, 18F-FLT, and 61Cu-ATSM PET in canine sinonasal tumors.

UNLABELLED: Intratumor heterogeneity in biologic properties and in relationships between various phenotypes may present a challenge for biologically targeted therapies. Understanding the relationships between different phenotypes in individual tumor types could help inform treatment selection. The goal of this study was to characterize spatial correlations of glucose metabolism, proliferation, and hypoxia in 2 histologic types of tumors. METHODS: Twenty canine veterinary patients with spontaneously occurring sinonasal tumors (13 carcinomas and 7 sarcomas) were imaged with (18)F-FDG, (18)F-labeled 3'-deoxy-3'-fluorothymidine ((18)F-FLT), and (61)Cu-labeled diacetyl-bis(N(4)-methylthiosemicarbazone) ((61)Cu-ATSM) PET/CT on 3 consecutive days. Precise positioning and immobilization techniques coupled with anesthesia enabled motionless scans with repeatable positioning. Standardized uptake values (SUVs) of gross sarcoma and carcinoma volumes were compared by use of Mann-Whitney U tests. Patient images were rigidly registered together, and intratumor tracer uptake distributions were compared. Voxel-based Spearman correlation coefficients were used to quantify intertracer correlations, and the correlation coefficients of sarcomas and carcinomas were compared. The relative overlap of the highest uptake volumes of the 3 tracers was quantified, and the values were compared for sarcomas and carcinomas. RESULTS: Large degrees of heterogeneity in SUV measures and phenotype correlations were observed. Carcinoma and sarcoma tumors differed significantly in SUV measures, with carcinoma tumors having significantly higher (18)F-FDG maximum SUVs than sarcoma tumors (11.1 vs. 5.0; P = 0.01) as well as higher (61)Cu-ATSM mean SUVs (2.6 vs. 1.2; P = 0.02). Carcinomas had significantly higher population-averaged Spearman correlation coefficients than sarcomas in comparisons of (18)F-FDG and (18)F-FLT (0.80 vs. 0.61; P = 0.02), (18)F-FLT and (61)Cu-ATSM (0.83 vs. 0.38; P < 0.0001), and (18)F-FDG and (61)Cu-ATSM (0.82 vs. 0.69; P = 0.04). Additionally, the highest uptake volumes of the 3 tracers had significantly greater overlap in carcinomas than in sarcomas. CONCLUSION: The relationships of glucose metabolism, proliferation, and hypoxia were heterogeneous across different tumors, with carcinomas tending to have high correlations and sarcomas having low correlations. Consequently, canine carcinoma tumors are robust targets for therapies that target a single biologic property, whereas sarcoma tumors may not be well suited for such therapies. Histology-specific PET correlations have far-reaching implications for the robustness of biologic target definition.

Feasibility and repeatability for in vivo measurements of stiffness gradients in the canine gastrocnemius tendon using an acoustoelastic strain gauge.

B-mode ultrasound is an established imaging modality for evaluating canine tendon injury. However, full extent of tendon injury often remains difficult to estimate, as small changes in sonographic appearance are associated with large changes in biomechanical strength. The acoustoelastic strain gauge (ASG) is an ultrasound-based tissue evaluation technique that relates the change in echo intensity observed during relaxation or stretching of tendons to the tissue's mechanical properties. This technique deduces stiffness gradient (the rate of change of normalized stiffness as a function of tissue strain) by analyzing the ultrasound dynamic images captured from gradually deforming tissue. ASG has been proven to accurately model strain and stiffness within tendons in vitro. To determine the feasibility and repeatability for in vivo ASG measurements of canine tendon function, stiffness gradients for the gastrocnemius tendons of 10 clinically normal dogs were recorded by two nonindependent observers at three sites (musculotendinous junction, mid tendon, and insertion). Average stiffness gradient indices (0.0132, 0.0141, 0.0136) and dispersion values (0.0053, 0.0054, 0.0057) for each site, respectively, were consistent with published mechanical properties for normal canine tendon. Mean differences of the average stiffness gradient index and dispersion value between observers and between limbs for each site were less than 16%. Using interclass coefficients (ICC), intra-observer (ICC 0.79-0.98) and interobserver (ICC 0.77-0.95) reproducibility was good to excellent. Right and left limb values were symmetric (ICC 0.74-0.92). Findings from this study indicated that ASG is a feasible and repeatable technique for measuring stiffness gradients in canine tendons.

Spatially resolved regression analysis of pre-treatment FDG, FLT and Cu-ATSM PET from post-treatment FDG PET: an exploratory study.

PURPOSE: To quantify associations between pre-radiotherapy and post-radiotherapy PET parameters via spatially resolved regression. MATERIALS AND METHODS: Ten canine sinonasal cancer patients underwent PET/CT scans of [(18)F]FDG (FDG(pre)), [(18)F]FLT (FLT(pre)), and [(61)Cu]Cu-ATSM (Cu-ATSM(pre)). Following radiotherapy regimens of 50 Gy in 10 fractions, veterinary patients underwent FDG PET/CT scans at 3 months (FDG(post)). Regression of standardized uptake values in baseline FDG(pre), FLT(pre) and Cu-ATSM(pre) tumour voxels to those in FDG(post) images was performed for linear, log-linear, generalized-linear and mixed-fit linear models. Goodness-of-fit in regression coefficients was assessed by R(2). Hypothesis testing of coefficients over the patient population was performed. RESULTS: Multivariate linear model fits of FDG(pre) to FDG(post) were significantly positive over the population (FDG(post) ~ 0.17 · FDG(pre), p = 0.03), and classified slopes of RECIST non-responders and responders to be different (0.37 vs. 0.07, p = 0.01). Generalized-linear model fits related FDG(pre) to FDG(post) by a linear power law (FDG(post) ~ FDG(pre)(0.93),p<0.001). Univariate mixture model fits of FDG(pre) improved R(2) from 0.17 to 0.52. Neither baseline FLT PET nor Cu-ATSM PET uptake contributed statistically significant multivariate regression coefficients. CONCLUSIONS: Spatially resolved regression analysis indicates that pre-treatment FDG PET uptake is most strongly associated with three-month post-treatment FDG PET uptake in this patient population, though associations are histopathology-dependent.