Single‐voxel and multi‐voxel spectroscopy yield comparable results in the normal juvenile canine brain when using 3 Tesla magnetic resonance imaging

Conventional magnetic resonance imaging (MRI) characteristics of canine brain diseases are often nonspecific. Single‐ and multi‐voxel spectroscopy techniques allow quantification of chemical biomarkers for tissues of interest and may help to improve diagnostic specificity. However, published information is currently lacking for the in vivo performance of these two techniques in dogs. The aim of this prospective, methods comparison study was to compare the performance of single‐ and multi‐voxel spectroscopy in the brains of eight healthy, juvenile dogs using 3 Tesla MRI. Ipsilateral regions of single‐ and multi‐voxel spectroscopy were performed in symmetric regions of interest of each brain in the parietal (n = 3), thalamic (n = 2), and piriform lobes (n = 3). In vivo single‐voxel spectroscopy and multi‐voxel spectroscopy metabolite ratios from the same size and multi‐voxel spectroscopy ratios from different sized regions of interest were compared. No significant difference was seen between single‐voxel spectroscopy and multi‐voxel spectroscopy metabolite ratios for any lobe when regions of interest were similar in size and shape. Significant lobar single‐voxel spectroscopy and multi‐voxel spectroscopy differences were seen between the parietal lobe and thalamus (P = 0.047) for the choline to N‐acetyl aspartase ratios when large multi‐voxel spectroscopy regions of interest were compared to very small multi‐voxel spectroscopy regions of interest within the same lobe; and for the N‐acetyl aspartase to creatine ratios in all lobes when single‐voxel spectroscopy was compared to combined (pooled) multi‐voxel spectroscopy datasets. Findings from this preliminary study indicated that single‐ and multi‐voxel spectroscopy techniques using 3T MRI yield comparable results for similar sized regions of interest in the normal canine brain. Findings also supported using the contralateral side as an internal control for dogs with brain lesions.     

DEVELOPMENT OF A WHOLE BODY MAGNETIC RESONANCE IMAGING PROTOCOL IN NORMAL DOGS AND CANINE CANCER PATIENTS

Whole body magnetic resonance imaging (whole body MR imaging) could potentially provide accurate cancer staging as a single imaging modality. This study was done to develop a whole body MR imaging protocol for a 1.5T MR instrument using four normal Beagle dogs (Phase 1) and then to assess the protocol's feasibility in cancer-bearing dogs (Phase II). In Phase I, anesthetized dogs were placed in dorsal recumbency with limbs flexed along the torso. T1, T2, and short tau inversion recovery sequences were acquired by spin echo or fast spin echo, and also using the more rapid single shot fast spin echo and gradient echo pulse sequences. Three large overlapping fields of view (FOV) were used to visualize the entire body and the sagittal and dorsal imaging planes were compared. Relative examination time, image quality, organ visibility and signal intensity were evaluated. Phase I results were used to establish a protocol that balanced image quality with examination time. In Phase II, whole body MR imaging was done on 10 dogs with cancer. Examination times were 60-75 min. Image quality was sufficient for all known lesions to be visualized, including mass lesions, pulmonary infiltrate, and lymphadenomegaly. Skeletal detail was sufficient to visualize known neoplastic lesions of the appendicular skeleton, yet it was suboptimal because of the large FOV and use of the body coil. Additional modifications of a whole body MR imaging protocol and continued technological improvements in MR imaging will further increase its potential for veterinary cancer staging.     

MAGNETIC RESONANCE IMAGING OF THE CANINE BRAIN AT 3 AND 7 T

Magnetic resonance (MR) imaging of the canine brain is commonly acquired at field strengths ranging from 0.2 to 1.5 T. Our purpose was to compare the MR image quality of the canine brain acquired at 3 vs. 7 T in dogs. Low‐resolution turbo spin echo (TSE) T2‐weighted images (T2W) were obtained in transverse, dorsal, and sagittal planes, and high‐resolution TSE T2W and turbo spin echo proton density‐weighted images were obtained in the transverse and dorsal planes, at both 3 and 7 T. Three experienced reviewers evaluated 32 predetermined brain structures independently and without knowledge of field strength for spatial resolution and contrast. Overall image quality and evidence of artifacts were also evaluated. Contrast of gray and white matter was assessed quantitatively by measuring signal intensity in regions of interest for transverse plane images for the three pulse sequences obtained. Overall, 19 of the 32 neuroanatomic structures had comparable spatial resolution and contrast at both field strengths. The overall image quality for low‐resolution T2W images was comparable at 3 and 7 T. High‐resolution T2W was characterized by superior image quality at 3 vs. 7 T. Magnetic susceptibility and chemical shift artifacts were slightly more noticeable at 7 T. MR imaging at 3 and at 7 T provides high spatial resolution and contrast images of the canine brain. The use of 3 and 7 T MR imaging may assist in the elucidation of the pathogenesis of brain disorders, such as epilepsy.     

COMPARISON BETWEEN PROTON MAGNETIC RESONANCE SPECTROSCOPY FINDINGS IN DOGS WITH TICK‐BORNE ENCEPHALITIS AND CLINICALLY NORMAL DOGS

In vivo diagnosis of tick‐borne encephalitis is difficult due to high seroprevalence and rapid viral clearance, limiting detection of antibodies in blood and cerebrospinal fluid. Magnetic resonance imaging (MRI) characteristics of tick‐borne encephalitis have been reported, however MRI studies can also be negative despite the presence of neurologic signs. Magnetic resonance spectroscopy (¹H MRS) is an imaging method that provides additional information about the metabolic characteristics of brain tissues. The purpose of this retrospective cross‐sectional study was to describe brain metabolites using short echo time single‐voxel ¹H MRS in dogs with confirmed tick‐borne encephalitis and compare them with healthy dogs. Inclusion criteria for the affected dogs were neurological symptoms suggestive of tick‐borne encephalitis, previous endemic stay and tick‐bite, diagnostic quality brain MRI and ¹H MRS studies, and positive antibody titers or confirmation of tick‐borne encephalitis with necropsy. Control dogs were 10, clinically normal beagles that had been used in a previous study. A total of six affected dogs met inclusion criteria. All dogs affected with tick‐borne encephalitis had ¹H MRS metabolite concentration alterations versus control dogs. These changes included mild to moderate decreases in N‐acetyl aspartate and creatine peaks, and mild increases in glutamate/glutamine peaks. No lactate or lipid signal was detected in any dog. Myoinositol and choline signals did not differ between affected and control dogs. In conclusion, findings supported the use of ¹H MRS as an adjunctive imaging method for dogs with suspected tick‐borne encephalitis and inconclusive conventional MRI findings.     

APPEARANCE OF THE CANINE MENINGES IN SUBTRACTION MAGNETIC RESONANCE IMAGES

The canine meninges are not visible as discrete structures in noncontrast magnetic resonance (MR) images, and are incompletely visualized in T1‐weighted, postgadolinium images, reportedly appearing as short, thin curvilinear segments with minimal enhancement. Subtraction imaging facilitates detection of enhancement of tissues, hence may increase the conspicuity of meninges. The aim of the present study was to describe qualitatively the appearance of canine meninges in subtraction MR images obtained using a dynamic technique. Images were reviewed of 10 consecutive dogs that had dynamic pre‐ and postgadolinium T1W imaging of the brain that was interpreted as normal, and had normal cerebrospinal fluid. Image‐anatomic correlation was facilitated by dissection and histologic examination of two canine cadavers. Meningeal enhancement was relatively inconspicuous in postgadolinium T1‐weighted images, but was clearly visible in subtraction images of all dogs. Enhancement was visible as faint, small‐rounded foci compatible with vessels seen end on within the sulci, a series of larger rounded foci compatible with vessels of variable caliber on the dorsal aspect of the cerebral cortex, and a continuous thin zone of moderate enhancement around the brain. Superimposition of color‐encoded subtraction images on pregadolinium T1‐ and T2‐weighted images facilitated localization of the origin of enhancement, which appeared to be predominantly dural, with relatively few leptomeningeal structures visible. Dynamic subtraction MR imaging should be considered for inclusion in clinical brain MR protocols because of the possibility that its use may increase sensitivity for lesions affecting the meninges.     

MAGNETIC RESONANCE ARTHROGRAPHY OF THE CANINE STIFLE JOINT TECHNIQUE AND APPLICATIONS IN ELEVEN MILITARY DOGS

The stifle joints of eleven military working dogs were evaluated using conventional magnetic resonance (MR) imaging and MR arthrography. A protocol optimizing MR imaging of the canine stifle joint is discussed, as well as potential uses for administration of intra-articular gadolinium. The technique for performing MR arthrography is described, and post-contrast image findings are reviewed. MR arthrography was performed by using an intra-articular injection of diluted gadolinium. Consistently good quality images were obtained, and no complications were clinically detected following MR arthrography. Cranial cruciate ligament abnormalities were seen in six dogs, meniscal abnormalities were visualized in nine menisci, and synovitis and medial ligament strain were seen in eight dogs. Surgical and post-mortem confirmation of these findings is discussed in seven dogs. Although MR arthrography adds an invasive procedure to conventional MR imaging, it can provide useful information on pathologic changes in the canine stifle joint.     

MAGNETIC RESONANCE IMAGING OF INTRACRANIAL INFLAMMATORY CONDITIONS IN DOGS: SENSITIVITY OF SUBTRACTION IMAGES VERSUS PRE‐ AND POST‐GADOLINIUM T1‐WEIGHTED IMAGE PAIRS

Ante mortem diagnosis of canine meningoencephalitis is usually based on the results of neurologic examination, cerebrospinal fluid analysis and magnetic resonance (MR) imaging. It has been hypothesized that subtraction MR imaging may increase the sensitivity of MR for intracranial inflammatory lesions compared to conventional post‐gadolinium T1‐weighted imaging. Sensitivity of pre‐ and post‐gadolinium (C‐/C+) image pairs and dynamic subtraction (DS) images was compared in a retrospective diagnostic accuracy study of 52 dogs with inflammatory cerebrospinal fluid and 67 dogs with idiopathic epilepsy. Series of transverse C‐/C+ and DS images were reviewed independently for signs of abnormal enhancement affecting the pachymeninges, leptomeninges or intra‐axial structures. Sensitivity of C‐/C+ image pairs and DS images was 48% (95% CI: 35–61%) and 65% (95% CI: 52–77%), respectively (P = 0.01). Intra‐axial lesions were observed more frequently than meningeal lesions in both C‐/C+ (43% vs. 31%) and DS images (61% vs. 22%). The difference in sensitivities of C‐/C+ and DS series was entirely due to increased sensitivity of DS images for intra‐axial lesions. Eight (12%) dogs with epilepsy had evidence of intra‐axial gadolinium accumulation affecting the cerebral cortex in DS images. This finding may represent a false‐positive result or a true sign of pathology, possibly associated with a leaky blood–brain barrier in areas of the brain affected by neovascularization secondary to repeated seizures. Results suggest that DS imaging has higher sensitivity than comparison of pre‐ and post‐gadolinium image pairs for inflammatory intra‐axial lesions.     

MAGNETIC RESONANCE IMAGING FEATURES OF INTRACRANIAL GRANULAR CELL TUMORS IN SIX DOGS

Magnetic resonance (MR) imaging characteristics of intracranial granular cell tumors (GCTs) have been previously reported in three dogs. The goal of this retrospective study was to examine a larger number of dogs and determine whether distinctive MR characteristics of intracranial GCTs could be identified. Six dogs with histologically confirmed intracranial GCTs and MR imaging were included. Tumor location, size, mass effect, T1‐ and T2‐weighted signal intensity, and peritumoral edema MR characteristics were recorded. In all dogs, GCTs appeared as well‐defined, extra‐axial masses with a plaque‐form, sessile distribution involving the meninges. All tumors were located along the convexity of the cerebrum, the falx cerebri, or the ventral floor of the cranial vault. All tumors were mildly hyperintense on T1‐weighted images, and iso‐ to hyperintense on T2‐weighted images. A moderate‐to‐severe degree of peritumoral edema and mass effect were evident in all dogs. Findings indicated that, while several MR imaging characteristics were consistently identified in canine cerebral GCTs, none of these characteristics were unique or distinctive for this tumor type alone.     

HEPATIC AND PANCREATICOBILIARY MRI AND MR CHOLANGIOPANCREATOGRAPHY WITH AND WITHOUT SECRETIN STIMULATION IN NORMAL CATS

Magnetic resonance (MR) cholangiopancreatography is useful in humans to diagnose biliary and pancreatic diseases. Some of these protocols incorporate the use of secretin, which stimulates the exocrine pancreas to release bicarbonate with secondary dilation of the pancreatic duct. We compared the utility and quality of multiple hepatic‐pancreaticobiliary MR imaging sequences before and after secretin stimulation of the pancreatic duct in five healthy cats. Multiple MR sequences were evaluated, including fast Spoiled Gradient Recalled in‐ and out‐of‐phase, Single Shot Fast Spin Echo (SSFSE), T2 Fast Spin Echo, MR cholangiopancreatography (pre‐ and postsecretin administration), and Fast Acquisition with Multiphase Efgre (FAME) (postsecretin and before and after gadolinium administration). The MR cholangiopancreatography protocol with secretin stimulation was feasible and yielded high‐contrast maps of the biliary ductal anatomy but the pancreactic duct was seen inconsistently. The FAME series most consistently provided visualization of biliary and postsecretin pancreatic ductal anatomy, combined with very good depiction of the liver and pancreas. The remaining sequences each had satisfactory utility and diagnostic quality, with the exception of the SSFSE sequences. Secretin improved the conspicuity of the pancreatic duct.     

Magnetic resonance spectroscopy of the canine brain at 3.0 T and 7.0 T

The purpose of this study was to evaluate the feasibility of proton magnetic resonance spectroscopy (1H MRS) to study the concentration of metabolites in the brain of dogs at 3.0 and 7.0 T. Four healthy male beagles were scanned using 3.0 T and 7.0 T human magnetic resonance imaging (MRI) units. The results obtained showed that all dogs had excellent quality spectra for a small (1 cm3) and large (8 cm3) voxel at 3.0 T, whereas only 2 dogs had high quality spectra at 7.0 T due to insufficient water suppression. 1H MRS at 3.0 T appears to be a reliable method to study metabolite concentrations in the canine brain. The development of more advanced water suppression techniques is necessary to improve the results at 7.0 T.     

LOW-FIELD MAGNETIC RESONANCE IMAGING OF BEAGLE BRAIN WITH A DEDICATED RECEIVER COIL

A specially designed radio frequency receiver coil was used in a low-field-strength (0.1 T) magnetic resonance imager to improve the image quality of the Beagle brain. The aim was to obtain better distinction of anatomic details with a better signal-to-noise ratio in shorter imaging time. The spin-echo (TR/TE = 1200/100; TR is the repetition time and TE is the echo time in ms) brain images of three Beagles indicate that the new receiver coil can fulfill these goals.     

Gadolinium contrast medium administration does not adversely affect T2*‐weighted gradient recalled echo magnetic resonance imaging of the canine brain at 1.5 Tesla

As gadolinium‐based contrast agents are paramagnetic and have T2 shortening effects, they have the potential to adversely affect gradient recalled echo sequences. The aim of this prospective, cross‐sectional study was to evaluate the effects of gadolinium administration on T2*‐weighted sequence diagnostic quality and signal intensity when imaging the canine brain. A total of 100 dogs underwent brain magnetic resonance imaging (MRI) including pre‐ and postcontrast T2*‐weighted sequences acquired with a delay (Group A) or immediately (Group B) following gadolinium administration. Pre‐ and postcontrast images were subjectively compared. In dogs with intracranial enhancing masses, regions of interest were drawn on corresponding images and signal intensity ratios were calculated. The effect of degree and pattern of contrast enhancement, susceptibility artifacts, and time between contrast injection and T2*‐weighted sequence acquisition on signal intensity ratio was evaluated. Overall 31 dogs had contrast enhancing intracranial masses. Subjectively, there was no difference in image quality of T2*‐weighted sequences obtained before and after contrast medium administration. No significant signal intensity differences of intracranial contrast enhancing masses were found (Group A P = 0.9999; Group B P = 0.9992). Susceptibility artifacts did not differ in appearance, and there was no effect on calculated signal intensity ratio (P = 0.8142). Similarly, there was no effect of degree of enhancement or contrast heterogeneity on signal intensity ratio (P = 0.4413). No correlation was found between signal intensity ratio and the time to acquisition (P = 0.199). Administration of gadolinium‐based MRI contrast agents does not adversely affect T2*‐weighted imaging of the brain in dogs at 1.5 T even in the presence of contrast enhancing lesions.     

CANINE MENINGEAL DISEASE: ASSOCIATIONS BETWEEN MAGNETIC RESONANCE IMAGING SIGNS AND HISTOLOGIC FINDINGS

In order to compare the accuracy of MR sequences for diagnosis of meningeal disease, MR images of the brain, and histopathologic specimens including the meninges of 60 dogs were reviewed retrospectively by independent observers in a cross‐sectional study. MR images included T1‐weighted pre‐ and postgadolinium images, subtraction images, T2‐weighted images, and T2‐weighted fluid‐attenuated inversion‐recovery (FLAIR) images. Pathologic changes affected the pachymeninges in 16 dogs, leptomeninges in 35 dogs, and brain in 38 dogs. The meninges were normal in 12 dogs. Meninges were classified histopathologically as normal (grade 0), slightly or inconsistently affected (grade 1), or markedly affected (grade 2). When applying relaxed pathologic criteria (grades 0 and 1 considered normal), the results of ROC analysis (area under curve, AUC) were: T1‐weighted postcontrast images 0.74; subtraction images 0.7; T2‐weighted images 0.68; FLAIR images 0.56. The difference in AUC between T1‐weighted postgadolinium images and FLAIR images was significant (P = 0.04). AUC for FLAIR images was not significantly different from 0.5. When applying strict pathologic criteria (only grade 0 considered normal), none of the MR sequences had AUC significantly different from 0.5. On the basis of T1‐weighted postgadolinium images and subtraction images, correct anatomic classification of lesions occurred more often for pachymeningeal than leptomeningeal lesions (P < 0.001). Overall, MR imaging had low sensitivity for diagnosis of meningeal pathology in dogs, particularly for changes affecting the leptomeninges. Subtraction images had similar accuracy to T1‐weighted postgadolinium images for meningeal lesions in dogs. T2‐weighted FLAIR images appear to have limited diagnostic utility for meningeal lesions.     

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.     

CONTRAST AGENT Gd‐EOB‐DTPA (EOB·Primovist®) FOR LOW‐FIELD MAGNETIC RESONANCE IMAGING OF CANINE FOCAL LIVER LESIONS

Contrast‐enhanced magnetic resonance (MR) imaging with a new liver‐specific contrast agent gadolinium‐ethoxybenzyl‐diethylenetriamine penta‐acetic acid (Gd‐EOB‐DTPA; EOB·Primovist®) was studied in 14 normal beagles and 9 dogs with focal liver lesions. Gd‐EOB‐DTPA accumulates in normally functioning hepatocytes 20 min after injection. As with Gd‐DTPA, it is also possible to perform a dynamic multiphasic examination of the liver with Gd‐EOB‐DTPA, including an arterial phase and a portal venous phase. First, a reliable protocol was developed and the appropriate timings for the dynamic study and the parenchymal phase in normal dogs using Gd‐EOB‐DTPA were determined. Second, the patterns of these images were evaluated in patient dogs with hepatic masses. The optimal time of arterial imaging was from 15 s after injection, and the optimal time for portal venous imaging was from 40 s after injection. Meanwhile, the optimal time to observe changes during the hepatobiliary phase was from 20 min after injection. In patient dogs, 11 lesions were diagnosed as malignant tumors; all were hypointense to the surrounding normal liver parenchyma during the hepatobiliary phase. Even with a low‐field MR imaging unit, the sequences afforded images adequate to visualize the liver parenchyma and to detect tumors within an appropriate scan time. Contrast‐enhanced MR imaging with Gd‐EOB‐DTPA provides good demarcation on low‐field MR imaging for diagnosing canine focal liver lesions.     

COMPARISON OF FAST SPIN-ECHO AND CONVENTIONAL SPIN-ECHO MAGNETIC RESONANCE SPINAL IMAGING TECHNIQUES IN FOUR NORMAL DOGS

Various magnetic resonance (MR) imaging techniques have been used to assess lumbar spinal abnormalities in people. Four, young adult, clinically normal dogs were used to compare images of the spinal cord acquired using conventional spin-echo and rapid acquisition relaxation-enhanced (RARE), commonly called fast spin-echo (FSE), magnetic resonance imaging techniques. Lateral myelograms were made as an anatomic control. The T2-weighted FSE technique was characterized by better image quality than the T2-weighted conventional spin-echo technique. The short acquisition time with the FSE technique allowed increases in the matrix size and number of excitations, thus improving resolution and signal-to-noise ratio. In canine lumbar spinal MR imaging, use of a FSE technique is recommended to reduce the overall time for imaging and to improve image quality.     

Treatment of canine nasopharyngeal stenosis using balloon‐expandable metallic stents: long‐term follow‐up of four cases

Four dogs were diagnosed with nasopharyngeal stenosis using e ndoscopy and magnetic resonance imaging. Treatment using balloon‐expandable metallic stent, placed under fluoroscopic and endoscopic guidance, resulted in immediate resolution of clinical signs. All dogs were clinically normal 40 to 62 months following stent placement.     

EVALUATION OF STANDARD MAGNETIC RESONANCE CHARACTERISTICS USED TO DIFFERENTIATE NEOPLASTIC,INFLAMMATORY, AND VASCULAR BRAIN LESIONS IN DOGS

Magnetic resonance (MR) imaging characteristics are commonly used to help predict intracranial disease categories in dogs, however, few large studies have objectively evaluated these characteristics. The purpose of this retrospective study was to evaluate MR characteristics that have been used to differentiate neoplastic, inflammatory, and vascular intracranial diseases in a large, multi‐institutional population of dogs. Medical records from three veterinary teaching hospitals were searched over a 6‐year period for dogs that had diagnostic quality brain MR scans and histologically confirmed intracranial disease. Three examiners who were unaware of histologic diagnosis independently evaluated 19 MR lesion characteristics totaling 57 possible responses. A total of 75 dogs with histologically confirmed intracranial disease were included in analyses: 51 with neoplasia, 18 with inflammatory disease, and six with cerebrovascular disease. Only strong contrast enhancement was more common in neoplasia than other disease categories. A multivariable statistical model suggested that extra‐axial origin, T2‐FLAIR mixed intensity, and defined lesion margins were also predictive of neoplasia. Meningeal enhancement, irregular lesion shape, and multifocal location distinguished inflammatory diseases from the other disease categories. No MR characteristics distinguished vascular lesions and these appeared most similar to neoplasia. These results differed from a previous report describing seven MR characteristics that were predictive of neoplasia in dogs and cats. Findings from the current study indicated that the high performance of MR for diagnosing canine intracranial diseases might be due to evaluator recognition of combinations of MR characteristics vs. relying on any one MR characteristic alone.