Comparison of ultrasonography, computed tomography, and single-photon emission computed tomography for the detection and localization of canine insulinoma

Accurate preoperative detection, localization, and staging of the primary tumor and metastases are essential for the selection of appropriate candidates for surgery. In dogs with insulinoma, preoperative assessment usually is performed with transabdominal ultrasonography (US). There are no reports on the use of computed tomography (CT) for this purpose. The preoperative use of somatostatin receptor scintigraphy (SRS) recently has been advocated for the identification of insulinoma and gastrinoma in dogs, but its accuracy remains to be established. In this report US, CT, and single-photon emission computed tomography (SPECT) with [111In-DTPA-D-Phe1]-octreotide (a specific form of SRS) were compared for their effectiveness in detecting and localizing primary and metastatic insulinoma in dogs. Findings at surgery or postmortem examination served as control. Of 14 primary insulinomas, 5, 10, and 6 were correctly identified by US, CT, and SPECT, respectively. No lymph node metastases were detected by US or SPECT. CT identified 2 of 5 lymph node metastases but also identified 28 false-positive lesions. Two of 4 livers were found to be positive for metastases by 1 of the imaging techniques. US can be used for the initial evaluation of dogs with hypoglycemia. Although CT identifies most primary tumors, intraoperative inspection and palpation of the pancreas is still superior. SPECT appears as effective as US and CT in detecting insulinomas. Future developments in preoperative imaging techniques might improve current methods of canine insulinoma detection.     

18F‐FDG‐PET/CT as adjunctive diagnostic modalities in canine fever of unknown origin

Fever of unknown origin (FUO) is a persistent or recurrent fever for which the underlying source has not been identified despite diagnostic investigation. In people, ¹⁸F‐fluoro‐2‐deoxyglucose positron emission tomography (¹⁸F‐FDG‐PET) alone or in combination with computed tomography (CT) is often beneficial in detecting the source of fever when other diagnostics have failed. Veterinary reports describing use of these modalities in animals with fever of unknown origin are currently lacking. Aims of this retrospective case series were to describe ¹⁸F‐FDG‐PET or ¹⁸F‐FDG‐PET/CT findings in a group of dogs with fever of unknown origin. Dogs presenting to a single center between April 2012 and August 2015 were included. A total of four dogs met inclusion criteria and underwent either positron emission tomography (n = 2) or positron emission tomography/CT (n = 2) as a part of their diagnostic investigation. All subjects underwent extensive diagnostic testing prior to ¹⁸F‐FDG‐PET/CT. Initial diagnostic evaluation failed to identify either a cause of fever or an anatomic location of disease in these four dogs. In each dog, positron emission tomography or positron emission tomography/CT was either able to localize or rule out the presence of focal lesion thereby allowing for directed sampling and/or informed disease treatment. Follow up ¹⁸F‐FDG‐PET/CT scans performed in two patients showed improvement of observed abnormalities (n = 1) or detected recurrence of disease allowing for repeated treatment before clinical signs recurred (n = 1). Fever resolved after specific treatment in each dog. Findings from the current study supported the use of positron emission tomography or positron emission tomography/CT as adjunctive imaging modalities for diagnosis and gauging response to therapy in dogs with fever of unknown origin.     

PET/CT today and tomorrow in veterinary cancer diagnosis and monitoring: fundamentals,early results and future perspectives

Functional imaging using positron emission tomography (PET) plays an important role in the diagnosis, staging, image‐guided treatment planning and monitoring of malignant diseases. PET imaging complements conventional anatomical imaging such as computed tomography (CT) and magnetic resonance imaging (MRI). The strength of CT scanning lies in its high spatial resolution, allowing for anatomical characterization of disease. PET imaging, however, moves beyond anatomy and characterizes tissue based on functions such as metabolic rate. Combined PET/CT scanners were introduced commercially in 2001 and a number of technological advancements have since occurred. Radiolabelled tracers such as ¹⁸F‐fluorodeoxyglucose (FDG) and ¹⁸F‐fluorothymidine (FLT) allow visualization of various metabolic processes within cancer cells. Many studies in human oncology evaluating the utility of PET/CT have demonstrated clinical benefits. Few veterinary studies have been performed, but initial studies show promise for improved detection of malignancy, more thorough staging of canine cancer and determination of early response and disease recrudescence.     

FDG PET/CT IMAGING IN CANINE CANCER PATIENTS

2‐Deoxy‐2‐[¹⁸F]fluoro‐d ‐glucose positron emission tomography/computed tomography (FDG PET/CT) is becoming increasingly available as an imaging modality in veterinary medicine. The purpose of this study was to report semiquantitative standard uptake values (SUV) of malignant and nonmalignant tissues and organs in canine cancer patients. FDG PET/CT was performed in 14 dogs including, nine mesenchymal tumors, four carcinomas, and one incompletely excised mast cell tumor. A generally higher FDG uptake was observed in carcinomas relative to sarcomas. Maximum SUV of carcinomas ranged from 7.6 to 27.0, and for sarcomas from 2.0 to 10.6. The FDG SUV of several organs and tissues, including regional brain uptake is reported, to serve as a reference for future FDG PET studies in canine cancer patients. Several potential pitfalls have been recognized in interpretation of FDG PET images of human patients, a number of these were also observed in this study.     

REVIEW OF DIAGNOSTIC IMAGING OF EAR DISEASES IN THE DOG AND CAT

Diagnostic imaging techniques (conventional radiography, computed tomography and magnetic resonance imaging) are an essential tool in the diagnostic work-up of ear diseases. Conventional radiography is commonly used, but often lacks sensitivity. Computed tomography (CT) and magnetic resonance (MR) are complementary imaging studies of the middle ear, labyrinth, internal auditory canal and their contents. CT provides excellent images of bony structures and is indicated where osseous changes are of greatest diagnostic importance. MR is superior in imaging soft tissue components including intralabyrinthine fluid. Therefore, more than one of these imaging techniques may be required in order to make a diagnosis.     

IMAGING DIAGNOSIS—MULTICENTRIC LYMPHOMA OF GRANULAR LYMPHOCYTES IMAGED WITH FDG PET/CT IN A DOG

A 5‐year‐old female spayed bulldog was referred for mild dyspnea, decreased activity and appetite, occasional nonproductive cough, polydipsia, and polyuria. A 2‐deoxy‐2‐[¹⁸F]fluoro‐D‐glucose (FDG) positron emission tomography/computed tomography (PET/CT) scan revealed unexpected activity in the heart, lungs, and mild generalized lymphadenopathy that led to the diagnosis of lymphoma of granular lymphocytes after nonspecific findings on imaging with standard modalities of echocardiography, thoracic radiography, and abdominal ultrasound. PET/CT scanning is a useful whole body imaging modality with high sensitivity for changes associated with canine lymphoma.     

PHYSIOLOGIC VARIANTS,BENIGN PROCESSES,AND ARTIFACTS FROM 106 CANINE AND FELINE FDG‐PET/COMPUTED TOMOGRAPHY SCANS

18F‐Fluoro‐deoxyglucose positron emission computed tomography (FDG‐PET/CT) is an emerging diagnostic imaging modality in veterinary medicine; however, little published information is available on physiologic variants, benign processes, and artifacts. The purpose of this retrospective study was to describe the number of occurrences of non‐neoplastic disease‐related FDG‐PET/CT lesions in a group of dogs and cats. Archived FDG‐PET/CT scans were retrieved and interpreted based on a consensus opinion of two board‐certified veterinary radiologists. Non‐neoplastic disease‐related lesions were categorized as physiologic variant, benign activity, or equipment/technology related artifact. If the exact cause of hypermetabolic areas could not be determined, lesions were put into an indeterminate category. A total of 106 canine and feline FDG‐PET/CT scans were included in the study. In 104 of the 106 scans, a total of 718 occurrences of physiologic variant, areas of incidental benign activity, and artifacts were identified. Twenty‐two of 23 feline scans and 82 of 83 canine scans had at least one artifact. Previously unreported areas of increased radiopharmaceutical uptake included foci associated with the canine gall bladder, linear uptake along the canine mandible, and focal uptake in the gastrointestinal tract. Benign activity was often seen and related to healing, inflammation, and indwelling implants. Artifacts were most often related to injection or misregistration. Further experience in recognizing the common veterinary FDG physiologic variation, incidental radiopharmaceutical uptake, and artifacts is important to avoid misinterpretation and false‐positive diagnoses.     

IMAGING OF PHEOCHROMOCYTOMA IN 2 DOGS USING p-[18F] FLUOROBENZYLGUANIDINE

p-[18F]Fluorobenzylguanidine ([18F]PFBG) is a norepinephrine analog that has been developed as a positron emission tomography (PET) imaging radiopharmaceutical. Myocardial sympathetic innervation, neuroendocrine structures, and tumors can be noninvasively imaged with [18F]PFBG. In this study, the uptake characteristics of [18F]PFBG were investigated in 2 dogs with a spontaneous pheochromocytoma. The extent of the pheochromocytoma was well documented in both dogs on the PET study. The standardized uptake values within the pheochromocytomas were greater than 25 by 10 min, and were 37 and 50 by 45 min in each dog. A third dog that was suspected to have an adrenal mass was also studied. In this dog, the [18F]PFBG study was normal. Surgical exploration and adrenal biopsy confirmed the [15F]PFBG imaging findings in both dogs. In each dog, there was rapid blood-pool clearance (within 10 min after intravenous administration of the [18F]PFBG), with high uptake specific within the myocardium and adrenal medulla. The results indicate that [18F]PFBG may be useful for imaging canine pheochromocytomas and aid in differentiating adrenal masses.     

Trends in veterinary cancer imaging

With the recent advances in diagnostic imaging technology, cancer imaging in veterinary medicine has become more specific for disease diagnosis, more accurate for determining tumour margins and more sensitive for detecting metastatic disease. Ultrasound provides highly detailed images of parenchymal masses and infiltrative lesions while providing a means for aspiration or biopsy using real‐time image guidance. Computed tomography and magnetic resonance‐imaging techniques provide exquisite anatomical resolution that improves diagnostic accuracy, provides an accurate means of radiation or surgical treatment planning and a quantitative means for monitoring response to therapy. In addition to traditional anatomic imaging, new techniques are being developed for estimating functional parameters such as tumour perfusion, cell metabolism and gene expression. While conventional planar scintigraphy has been available for some time, newer nuclear imaging modalities such as positron emission tomography promise to further improve the accuracy of initial tumour diagnosis and staging and determination of response to therapy. Although many of these functional techniques are not yet clinically available, it is highly likely that some will be integrated into routine clinical practice in the near future.     

IMAGING: BONE*

Bone can be imaged by a variety of methods including survey radiography, stress radiography, contrast radiography, fluoroscopy, tomography, magnification radiography, xeroradiography, and nuclear imaging. Each of these imaging techniques and modalities is presented as it applies to diagnostic imaging of bone in veterinary medicine     

NORMAL REGIONAL DISTRIBUTION OF CEREBRAL BLOOD FLOW IN DOGS: COMPARISON BETWEEN 99mTc‐ETHYLCYSTEINATE DIMER AND 99mTc‐ HEXAMETHYLPROPYLENE AMINE OXIME SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY

Functional imaging provides important insights into canine brain pathologies such as behavioral problems. Two ^99mTc‐labeled single photon emission computed tomography (SPECT) cerebral blood flow tracers—ethylcysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO)—are commonly used in human medicine and have been used previously in dogs but intrasubject comparison of both tracers in dogs is lacking. Therefore, this study investigated whether regional distribution differences between both tracers occur in dogs as is reported in humans. Eight beagles underwent two SPECT examinations first with ^99mTc‐ECD and followed by ^99mTc‐HMPAO. SPECT scanning was performed with a triple head gamma camera equipped with ultrahigh resolution parallel hole collimators. Images were reconstructed using filtered backprojection with a Butterworth filter. Emission data were fitted to a template permitting semiquantification using predefined regions or volumes of interest (VOIs). For each VOI, perfusion indices were calculated by normalizing the regional counts per voxel to total brain counts per voxel. The obtained perfusion indices for each region for both tracers were compared with a paired Student's T‐test. Significant (P < 0.05) regional differences were seen in the subcortical region and the cerebellum. Both tracers can be used to visualize regional cerebral blood flow in dogs, however, due to the observed regional differences, they are not entirely interchangeable.     

REGIONAL BRAIN PERFUSION IN EPILEPTIC DOGS EVALUATED BY TECHNETIUM-99m-ETHYL CYSTEINATE DIMER SPECT

We evaluated the feasibility of interictal single photon emission computed tomography (SPECT) to detect alterations in regional cerebral blood flow and neuronal activity in dogs with idiopathic epilepsy. Twelve dogs with idiopathic epilepsy underwent interictal technetium-99m-ethyl cysteinate dimer SPECT of the brain. Different cortical regions of interest (ROIs), 1 ROI at the cerebellum and 1 ROI at the subcortical area were evaluated by semiquantitative analysis and compared with a control group (18 dogs). Significant hypoperfusion ( P =0.02) was present in the subcortical area of epileptic dogs. This hypoperfusion was not associated with seizure frequency, age at onset of seizures, duration of epilepsy, or time since the last seizure. Interictal SPECT did not reveal cortical or cerebellar perfusion alterations. The subcortical area may play an important role in the pathophysiology of canine idiopathic epilepsy.     

A REVIEW OF IMAGING TECHNIQUES FOR CANINE CAUDA EQUINA SYNDROME

There are many imaging modalities available for evaluating the canine lumbosacral region. These include conventional radiography, stress radiography, myelography, epidurography, transosseous and intravenous venography, discography, linear tomography, computed tomography, and magnetic resonance imaging. Myelography, epidurography and discography are commonly used, but often lack sensitivity. Myelography is of little value when evaluating the cauda equina because the dural sac is elevated from the vertebral canal floor and frequently ends before the lumbosacral junction. Epidurography will identify a ventrally located compressive lesion and discography can delineate the dorsal extent of the diseased disc; however, both are sometimes difficult to interpret. Therefore, more than one of these imaging techniques must be used in order to make a diagnosis. Computed tomography and magnetic resonance imaging have become valuable in evaluating the lumbosacral region in dogs. These modalities have proven to be both sensitive and specific for determining cauda equina compression in both humans and in dogs.     

Advanced imaging for veterinary cancer patients.

This article presents an update on the recent advances made in veterinary advanced imaging specifically with regard to cross-sectional modalities (CT and MRI) and nuclear medicine (positron emission tomography [PET] and PET/CT). A brief summary of technical improvements and a review of recent literature are included to provide an overview of the progress made in this important element of the practicing veterinary oncologist's repertoire. An in-depth summary of PET is also included to introduce the technical aspects and potential clinical and research applications of this novel imaging modality in veterinary medicine.     

IMAGING DIAGNOSIS—FDG‐PET/CT OF A CANINE SPLENIC PLASMA CELL TUMOR

An 8‐year‐old Shih Tzu developed abdominal pain and hyperglobulinemia. A round splenic mass was noted radiographically and sonographically. The patient was evaluated by fluorodeoxyglucose positron emission tomography coupled with computed tomography (FDG‐PET/CT). There was no evidence of metastasis or bone marrow involvement on PET/CT images. The standardized uptake value (SUV) of the splenic mass was increased over the reference range (SUV=4.83). The patient was diagnosed as splenic extramedullary plasmacytoma through immunohistopathologic study. After the splenectomy, the globulin level normalized and the patient is alive without complications.     

Effect of Harderian adenectomy on the statistical analyses of mouse brain imaging using positron emission tomography

Positron emission tomography (PET) using 2-deoxy-2-[¹⁸F] fluoro-D-glucose (FDG) as a radioactive tracer is a useful technique for in vivo brain imaging. However, the anatomical and physiological features of the Harderian gland limit the use of FDG-PET imaging in the mouse brain. The gland shows strong FDG uptake, which in turn results in distorted PET images of the frontal brain region. The purpose of this study was to determine if a simple surgical procedure to remove the Harderian gland prior to PET imaging of mouse brains could reduce or eliminate FDG uptake. Measurement of FDG uptake in unilaterally adenectomized mice showed that the radioactive signal emitted from the intact Harderian gland distorts frontal brain region images. Spatial parametric measurement analysis demonstrated that the presence of the Harderian gland could prevent accurate assessment of brain PET imaging. Bilateral Harderian adenectomy efficiently eliminated unwanted radioactive signal spillover into the frontal brain region beginning on postoperative Day 10. Harderian adenectomy did not cause any post-operative complications during the experimental period. These findings demonstrate the benefits of performing a Harderian adenectomy prior to PET imaging of mouse brains.     

Imaging: Nuclear*

In this paper an overview of principles involved in nuclear imaging is presented. Nuclear images are picotrial representations of the distribution of systemically administered radiopharmaceuticals. Although many radionuclides are available. ^99mTc is the most commonly used radionuclide, either in ionic form (^99mTcO₄) or bound to other pharmaceuticals. Distribution within the body is by physiologic processes, dependent on the radiopharmaceutical used. Most distribution processes are organ specific rather than disease specific. Scintillation detectors are used to record the activity and disribution of an administered radiopharmaceutical and to create a representative image on film. A rectilinear scanner is an imaging system with a small detector that moves systematically, point by point, over an organ of interest. A gamma (scintillation) camera is an imaging system with a large stationary detector that encompasses a larger field of view. Nuclear imaging provides information based primarily on physiologic principles, and radiography provides infromation based primarily on anatomic or geometric principles. Examples of some scanning procedures are discussed.     

Effects of medetomidine and ketamine on the regional cerebral blood flow in cats: a SPECT study

Brain perfusion can be investigated using single photon emission computed tomography (SPECT) and the intravenous injection of (99m)technetium ethyl cysteinate dimer ((99m)Tc-ECD). However, sedation using medetomidine, an α(2)-agonist, or anaesthesia using medetomidine and ketamine, an N-methyl-d-aspartate-(NMDA)-antagonist, may be required for SPECT studies in cats but can affect the regional cerebral blood flow (rCBF). The effects of medetomidine, with or without ketamine, on regional brain perfusion were therefore investigated in six cats under three conditions. Injection of tracer occurred before sedation or anaesthesia (condition A), following intramuscular (IM) sedation with medetomidine (condition M) or after IM anaesthesia with medetomidine and ketamine (condition MK). Medetomidine and medetomidine with ketamine caused a significantly higher total tracer uptake in all brain regions. Semi-quantification of brain perfusion gave lower perfusion indices in several sub-cortical regions in conditions M and MK, compared to A. Left-right differences were observed in the temporal cortex (A), the temporal, parietal cortex and the thalamus (M) and the frontal cortex (MK). A significantly higher perfusion index in the sub-cortical regions, compared to the whole cortex, was only present in condition A. This study showed that caution is needed when quantifying brain perfusion indices when using sedative or anaesthetic agents that may affect rCBF.     

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.