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 Both recipients were withdrawn from all IS and continued to maintain normal renal allograft function for 4 years without rejection or GVHD.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.

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.

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.

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.

Modified ear canal ablation and lateral bulla osteotomy for management of otitis media in an alpaca.

OBJECTIVE: To report surgical treatment of severe otitis media in an alpaca by a modification of a subtotal ear canal ablation and lateral bulla osteotomy technique used in dogs. STUDY DESIGN: Case report. ANIMALS: An 11-week-old female alpaca cria. METHODS: The cria had a 2-week history of right otitis media, nonresponsive to medical treatment, as well as right facial nerve paralysis, and a melting corneal ulcer of the right eye. Otitis media was confirmed by computed tomography. Right subtotal ear canal ablation and lateral bulla osteotomy were performed using a modification of a technique reported in dogs. RESULTS: There were no surgical complications and the alpaca was discharged from the hospital 5 days later. At 10 months, moderate motor function had been restored to the pinna with the ear standing partially erect. The otitis had resolved, and the alpaca was reportedly well integrated into the herd. CONCLUSION: Subtotal ear canal ablation and lateral bulla osteotomy, a technique modified from that performed in dogs, were successful in providing complete clinical resolution of otitis media in an alpaca.

Hydrocephalus in a yellow-headed Amazon parrot (Amazona ochrocephala oratrix).

A 37-year-old female yellow-headed Amazon parrot (Amazona ochrocephala oratrix) was presented after a 4-month-period behavior change and intermittent episodes of obtunded mentation. Clinical findings on physical examination included ataxia, a weak grasp, and reluctance to move. Results of magnetic resonance imaging were consistent with severe hydrocephalus without evidence of cerebrospinal fluid obstruction. The bird was treated with tapering dosages of prednisolone over a 4-month period, during which time the episodes did not occur. Discontinuation of treatment was attempted several times but resulted in relapse. After 3.5 years of maintenance treatment with prednisolone, the bird was presented subsequent to a 5-hour episode of obtunded mentation and worsening neurologic signs. Despite increasing the dose of prednisolone and providing additional supportive care, the bird's condition worsened, and euthanasia was elected. Necropsy findings included severe hydrocephalus with significant loss of right cerebral parenchyma and no evidence of cerebrospinal fluid obstruction. Histologic examination of the remaining cerebral parenchyma revealed a moderate, multifocal, cellular infiltrate; encephalomalacia; fibrosis; and hemosiderosis in tissue adjacent to the distended ventricles. Other findings included hepatic vacuolar degeneration. Diagnostic imaging and postmortem findings were consistent with a diagnosis of hydrocephalus ex vacuo. To our knowledge, this is the first report of hydrocephalus in an Amazon parrot as well as the first report of hydrocephalus in any avian species associated with long-term follow-up and prolonged corticosteroid treatment.

Concurrent occipital bone malformation and atlantoaxial subluxation in a neonatal harbor seal (Phoca vitulina).

A stranded male harbor seal (Phoca vitulina) neonate with progressive clinical signs of ataxia, tremors, and deteriorating consciousness was evaluated using magnetic resonance imaging for suspected cerebellar brain disease prior to euthanasia because of grave prognosis. Magnetic resonance imaging identified occipital bone dysplasia with cerebellar herniation and concurrent atlantoaxial subluxation with spinal cord compression. These imaging findings elucidated the cause of histopathology changes including gliosis of the cerebellum and axonal degeneration and dilation of myelin sheaths of the dorsal funiculus of the spinal cord. Occipital bone dysplasia and/ or atlantoaxial subluxation should be considered as differentials for abnormal neurologic signs in harbor seal neonates. Magnetic resonance imaging is a valuable modality for antemortem diagnosis.

Magnetic resonance imaging findings in dogs with confirmed shoulder pathology.

OBJECTIVE: To evaluate the diagnostic potential of magnetic resonance imaging (MRI) compared with a reference standard, arthroscopic and/or open surgery, in dogs with soft tissue shoulder pathology. STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n=21). METHODS: Magnetic resonance (MR) images were retrospectively evaluated in 21 dogs that had surgically identified soft tissue shoulder pathology. The musculotendinous units of the biceps, infraspinatus, teres minor, supraspinatus, subscapularis, and the medial and lateral glenohumeral ligaments (MGHL and LGHL) were graded as either normal or abnormal. Abnormal structures were further classified as being either inflamed, partially torn, or fully torn. Impingement of the biceps tendon was also evaluated. Results were reported in terms of agreement and concordance between MRI findings and surgical findings. Agreement was defined as the percentage of times MRI findings concurred with surgical findings with respect to a structure being either normal or abnormal. Concordance was defined as the percentage of times MRI concurred with the exact surgically assessed pathology when abnormality was identified. RESULTS: The findings were biceps tendon: 90% agreement with 100% concordance; subscapularis: 95% agreement with 62% concordance; MGHL: 84% agreement with 83% concordance; LGHL: 88% agreement with 100% concordance; infraspinatus: 100% both agreement and concordance; biceps tendon impingement: 90% agreement with 100% concordance. CONCLUSIONS: Soft tissue abnormalities of the canine shoulder were readily identified on preoperative MR images. CLINICAL RELEVANCE: MRI shows great potential as a diagnostic tool in the evaluation of canine shoulder disease.

Correlation of ultrasonographic appearance of lesions and cytologic and histologic diagnoses in splenic aspirates from dogs and cats: 32 cases (2002-2005).

OBJECTIVE: To determine the accuracy of cytologic diagnosis, compared with histologic diagnosis, in determination of disease in ultrasound-guided fine-needle aspirates of splenic lesions. DESIGN: Retrospective study. SAMPLE POPULATION: Splenic specimens from 29 dogs and 3 cats. PROCEDURES: Records were searched for dogs and cats that had undergone ultrasound-guided splenic aspiration. Criteria for inclusion were ultrasonographic identification of splenic lesions and cytologic and histologic evaluation of tissue from the same lesion. Cytologic samples were obtained by fine-needle aspiration, and histologic specimens were obtained via surgical biopsy, ultrasound-guided biopsy, or necropsy. RESULTS: Cytologic diagnoses corresponded with histologic diagnoses in 19 of 31 (61.3%) cases and differed in 5 of 31(16.1%) cases, and 1 aspirate was inadequate for evaluation. In 7 of 31 (22.6%) cases, histologic evaluation of tissue architecture was required to distinguish between reactive and neoplastic conditions. On the basis of histologic diagnosis in 14 animals with nonneoplastic conditions, the cytologic diagnosis was correct in 11 cases, not definitive in 2 cases, and incorrect in 1 case. In 17 animals with malignant neoplastic diseases, the cytologic diagnosis was correct in 8 cases, not definitive but consistent with possible neoplasia in 5 cases, and incorrect in 4 cases. Multiple similar-appearing nodules were significantly associated with malignancy, whereas single lesions were more often benign. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasound-guided aspiration of splenic lesions is a minimally invasive tool for obtaining specimens for cytologic evaluation. Although cytologic diagnoses often reflect histologic results, if missampling or incomplete sampling occurs or tissue architecture is required to distinguish between reactive and neoplastic conditions, accurate diagnosis with fine-needle aspiration may not be possible.

Intensity-modulated radiation therapy and helical tomotherapy: its origin, benefits, and potential applications in veterinary medicine.

Intensity-modulated radiation therapy (IMRT), especially image-guided IMRT as represented by helical tomotherapy, is a novel approach to therapy and is rapidly evolving. Both of these forms of therapy aim to allow targeted radiation delivery to the tumor volume while minimizing dose to the surrounding normal tissues. Adaptive radiation therapy and conformal avoidance are possible with intensity-modulated therapy and helical tomotherapy, which offer opportunities for improved local tumor control, decreased normal tissue toxicity, and improved survival and quality of life. Human and veterinary patients are likely to benefit from the continued development of this radiation delivery technique, and data over the next several years should be crucial in determining its true benefit.

Development of a retrobulbar injection technique for ocular surgery and analgesia in dogs.

OBJECTIVE: To develop and compare 3 techniques for retrobulbar injection of local anesthetic agents for ocular surgery and analgesia in dogs. DESIGN: Prospective study. ANIMALS: 17 dogs (including 9 cadavers). PROCEDURES: Inferior-temporal palpebral (ITP), perimandibular, and combined superior-inferior peribulbar injection techniques were compared by assessing the distribution of latex after injection into the orbits of 5 canine cadavers; magnetic resonance imaging (MRI) evaluation of the distribution of contrast agent after injection in the retrobulbar space of 4 canine cadavers; and assessment of the efficacy and MRI evaluation of the anatomic distribution of injections of a lidocainecontrast agent mixture in 4 anesthetized, nonrecovery dogs. By use of the preferred technique (ITP), the ocular effects of lidocaine anesthesia were evaluated in 4 dogs; during a 2-week period after treatment, dogs underwent ophthalmic examination, Schirmer tear testing (STT), intraocular pressure (IOP) measurement, and Cochet-Bonnet esthesiometry. RESULTS: Of the 3 techniques, the ITP technique was the preferred method for retrobulbar administration of anesthetic agent in dogs because it was efficacious (pupil dilation and central rotation of the globe achieved in all eyes), easiest to perform, and provided thorough coverage of the intraconal retrobulbar space without complication. During the 2-week follow-up period, the ITP injection did not significantly affect STT, IOP, or Cochet-Bonnet esthesiometry values in dogs. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, retrobulbar administration of anesthetic agents via the ITP technique is a potential alternative to systemic administration of neuromuscular blocking agents for ophthalmic surgery and provides the additional benefit of local ocular analgesia.

Radiation therapy for incompletely excised grade II canine mast cell tumors.

Forty-five dogs with incompletely excised grade II mast cell tumors were treated with radiation using a cobalt 60 teletherapy unit (15 fractions of 3.2 Gy for a total of 48 Gy). Twenty-four of the dogs underwent prophylactic regional lymph node irradiation. Three (6.7%) dogs had tumor recurrence, two (4.4%) dogs developed metastasis, and 14 (31%) dogs developed a second cutaneous mast cell tumor. No difference in overall survival rate was observed between the dogs receiving and not receiving prophylactic irradiation of the regional lymph node.

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.

Outcome of accelerated radiotherapy alone or accelerated radiotherapy followed by exenteration of the nasal cavity in dogs with intranasal neoplasia: 53 cases (1990-2002).

OBJECTIVE: To compare long-term results of radiotherapy alone versus radiotherapy followed by exenteration of the nasal cavity in dogs with malignant intranasal neoplasia. DESIGN: Retrospective study. ANIMALS: 53 dogs with malignant intranasal neoplasia. PROCEDURE: All dogs underwent radiotherapy consisting of administration of 10 fractions of 4.2 Gy each on consecutive weekdays. For dogs in the surgery group (n=13), follow-up computed tomography was performed, and dogs were scheduled for surgery if persistent or recurrent tumor was seen. RESULTS: Perioperative complications for dogs that underwent surgery included hemorrhage requiring transfusion (2 dogs) and subcutaneous emphysema (8). Rhinitis and osteomyelitis-osteonecrosis occurred significantly more frequently in dogs in the radiotherapy and surgery group (9 and 4 dogs, respectively) than in dogs in the radiotherapy-only group (4 and 3 dogs, respectively). Two- and 3-year survival rates were 44% and 24%, respectively, for dogs in the radiotherapy group and 69% and 58%, respectively, for dogs in the surgery group. Overall median survival time for dogs in the radiotherapy and surgery group (477 months) was significantly longer than time for dogs in the radiotherapy-only group (19.7 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that exenteration of the nasal cavity significantly prolongs survival time in dogs with intranasal neoplasia that have undergone radiotherapy. Exenteration after radiotherapy may increase the risk of chronic complications.

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.

The utility of megavoltage computed tomography images from a helical tomotherapy system for setup verification purposes.

PURPOSE: To evaluate the utility of relatively low-dose megavoltage computed tomography (MVCT) images from a clinical helical tomotherapy system for setup verification purposes. METHODS AND MATERIALS: Cross-sectional kilovolt computed tomography (kVCT) images were obtained for treatment planning purposes on a diagnostic third-generation CT scanner, followed by MVCT images from a helical tomotherapy system in 8 pet dogs with spontaneously occurring tumors. The kVCT and MVCT images were aligned for setup verification purposes, allowing repositioning before treatment delivery. RESULTS: Tumors are readily visualized on the MVCT images. At a dose of 2-3 cGy, the MVCT images are of sufficient quality for verification of treatment setup, but soft-tissue contrast is inferior to that with conventional kVCT. The MV and kVCT images were successfully aligned. When necessary, patients undergoing helical tomotherapy were repositioned before treatment. CONCLUSIONS: Megavoltage CT image quality is sufficient for tumor identification and three-dimensional setup verification in dogs with spontaneous tumors. The MVCT images can be aligned with the planning kVCT to ensure proper patient registration before treatment. Image alignment was successful in these canine patients, despite no skin markings defining patient positioning between the two scans. MVCT images facilitate setup verification, and their tomographic nature offers improvements over conventional portal imaging.

Piroxicam, mitoxantrone, and coarse fraction radiotherapy for the treatment of transitional cell carcinoma of the bladder in 10 dogs: a pilot study.

Ten dogs with transitional cell carcinoma (TCC) of the bladder were treated with a combination of once-weekly coarse fraction radiation therapy (six weekly fractions of 5.75 Gray [Gy]), mitoxantrone chemotherapy, and piroxicam. All dogs completed the radiation therapy protocol, and only minimal side effects were observed. Only two (22%) dogs achieved a measurable partial response; however, 90% of the dogs had amelioration of their urinary clinical signs. The median survival time for all dogs was 326 days. While this treatment protocol was well tolerated, the response rate and overall survival duration was not superior to reports using mitoxantrone and piroxicam without radiation therapy in dogs with TCC.

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.

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.

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.