Assessment of tumor hypoxia in spontaneous canine tumors after treatment with OMX, a novel H-NOX oxygen carrier, with [18F]FMISO PET/CT.

BACKGROUND: Hypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors. RESULTS: Thirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV. CONCLUSIONS: [18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.

Computed tomographic bronchial collapsibility values over 50% may be detected in healthy dogs.

Bronchomalacia and bronchial collapse are important causes of chronic coughing in dogs. The current reference standard diagnostic tests for these problems are flexible bronchoscopy and biopsy. Previous human studies have also supported inspiration/expiration computed tomography (CT) as a diagnostic test. The current prospective, pilot study aimed to determine whether inspiration/expiration CT is also a feasible test for quantifying bronchial collapsibility in dogs. Thoracic CT images were acquired using a 64-row multidetector CT for 10 healthy Beagle dogs during maximal inspiration and expiration. For each scan, one observer measured transverse sectional areas of the mainstem and lobar bronchi, and the dorsal and ventral segmental bronchi of the left cranial lobar bronchus. Diameters for each bronchus were also measured in transverse, sagittal, and dorsal planes. Bronchial collapsibility (%) was calculated as the difference between inspiration/expiration transverse sectional areas divided by the inspiration transverse sectional areas. Mean bronchial collapsibility of all bronchi was 38.20 ± 15.17%. A collapsibility of over 50% was found in the dorsal (n = 7) and ventral (n = 4) segmental bronchi of the left cranial lobar bronchus, and the left caudal (n = 5) and right middle (n = 2) lobar bronchus. Bronchial collapsibility measurements were greater in the dorsal and ventral segmental bronchi of the left cranial lobar bronchus and the left caudal lobar bronchus (P < 0.001). Findings supported inspiration/expiration CT as a modality to noninvasively assess bronchial collapse in dogs and a bronchial collapsibility value greater than 50% for detecting pathologic bronchial collapse in clinically affected dogs.

Kinetic Evaluation of the Hypoxia Radiotracers [18F]FMISO and [18F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging.

Purpose: We evaluated the kinetics of the hypoxia PET radiotracers, [18F]fluoromisonidazole ([18F]FMISO) and [18F]fluoroazomycin-arabinoside ([18F]FAZA), for tumor hypoxia detection and to assess the correlation of hypoxic kinetic parameters with static imaging measures in canine spontaneous tumors. Methods: Sixteen dogs with spontaneous tumors underwent a 150-min dynamic PET scan using either [18F]FMISO or [18F]FAZA. The maximum tumor-to-muscle ratio (TMRmax) > 1.4 on the last image frame was used as the standard threshold to determine tumor hypoxia. The tumor time-activity curves were analyzed using irreversible and reversible two-tissue compartment models and graphical methods. TMRmax was compared with radiotracer trapping rate (k 3), influx rate (K i), and distribution volume (V T). Results: Tumor hypoxia was detected in 7/8 tumors in the [18F]FMISO group and 4/8 tumors in the [18F]FAZA group. All hypoxic tumors were detected at > 120 min with [18F]FMISO and at > 60 min with [18F]FAZA. [18F]FAZA showed better fit with the reversible model. TMRmax was strongly correlated with the irreversible parameters (k 3 and K i) for [18F]FMISO at > 90 min and with the reversible parameter (V T) for [18F]FAZA at > 120 min. Conclusions: Our results showed that [18F]FAZA provided a promising alternative radiotracer to [18F]FMISO with detecting the presence of tumor hypoxia at an earlier time (60 min), consistent with its favorable faster kinetics. The strong correlation between TMRmax over the 90-150 min and 120-150 min timeframes with [18F]FMISO and [18F]FAZA, respectively, with kinetic parameters associated with tumor hypoxia for each radiotracer, suggests that a static scan measurement (TMRmax) is a good alternative to quantify tumor hypoxia. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-022-00780-4.

Suspected Cerebral Salt Wasting Syndrome with Cervical Spinal Lesion in a Domestic Shorthair Cat.

A 12-year-old spayed female domestic short cat was presented with tetraplegia. The cat also showed signs of hyponatremia and dehydration, which were rapidly corrected by intravenous fluid infusion. Based on thorough physical and neurological examinations, the patient was suspected of having an intracranial disease. MRI revealed a high-signal T2 image of the bilateral parietal cerebral cortical gray matter junction, which is associated with fast electrolyte calibration, and a high-signal T2 image of the C2 spinal cord ventral area, which is associated with ischemic myelopathy. The cat reappeared three days later due to anorexia. Laboratory examinations revealed that the cat was clinically dehydrated and exhibited hyponatremia. Other causes of hyponatremia were excluded through history-taking, laboratory examination, imaging, and therapeutic response to fluid therapy, except for cerebral salt-wasting syndrome (CSWS). The cat was discharged 3 days after the start of fludrocortisone therapy with electrolytes within the normal range. Magnetic resonance imaging (MRI) was performed again 1 month after hospitalization, and the cerebral lesion disappeared, but the spinal cord lesion worsened compared to the previous image. The patient was euthanized due to the progression of the spinal lesion, with a poor prognosis and poor quality of life. This is the first case of suspected CSWS with a cervical spinal lesion in a cat.

Off-Label Use of Crisdesalazine (GedaCure) in Meningoencephalitis in Two Dogs.

An 8-year-old, castrated male Shih-tzu dog (Case 1) showing ataxia and gait disorder was referred for neurological examination and magnetic resonance imaging. Through comprehensive examinations, the patient was tentatively diagnosed with meningoencephalitis of unknown origin (MUO) and treatment with prednisolone and cytosine arabinoside was started. The symptoms were improving with immunosuppressive treatment. However, severe bacterial cystitis occurred and we could not avoid tapering off prednisolone. Then, neurological signs recurred. Therefore, we added crisdesalazine, which allowed us to reduce the daily dosage of immunosuppressants easily. In another case, a 4-year-old, spayed female Yorkshire terrier dog (Case 2) was referred to our hospital showing a head tilt, circling, and loss of the menace reflex. The patient was tentatively diagnosed with MUO and treatment with some immunosuppressants was attempted. The clinical symptoms improved, but the alleviation was inadequate. Thus, we added crisdesalazine. The neurological signs then markedly improved. Moreover, the drugs could be tapered off more easily than before. Crisdesalazine is a novel drug that has antioxidant and anti-inflammatory action in brain disease and is used particularly for dementia. In this paper, we tried an off-label use of this drug in canine MUO patients, and found that it had, in these two patients, additional therapeutic effects on the MUO.

Positive-pressure breath-hold positron emission tomography/computed tomography is feasible for respiratory-induced artifact reduction in healthy dogs.

OBJECTIVE: To perform qualitative and quantitative analysis of positron emission tomography (PET)/CT images using spontaneous ventilation (SV) and positive-pressure breath-hold (PPBH) techniques in order to demonstrate the feasibility of PPBH PET/CT to decrease respiration-induced artifacts. ANIMALS: 5 healthy female mixed-breed dogs. PROCEDURES: 2-([18F]fluoro)-2-deoxy-D-glucose (was administered to each anesthetized dog. An SV PET/CT scan was performed from the head to the femur using 8 bed positions (3 min/bed) followed by a PPBH scan centered over the diaphragm with a single bed position (1.5 min/bed). PET image quality, the misalignment of organs between PET and CT images, and standardized uptake values (SUVs) of liver adjacent to diaphragm were compared between SV and PPBH. RESULTS: Overall image quality and conspicuity of anatomic structures were superior in PPBH than in SV PET images. PPBH induced significantly less misalignment of the liver and diaphragm in all planes compared to SV. For the gall bladder, PPBH showed significantly less misalignment than SV only in the transverse plane. The maximum SUV in all of the liver areas was significantly higher with PPBH compared to SV. PPBH exhibited significantly higher mean SUV in the liver adjacent to the left diaphragmatic dome and left lateral border and higher minimum SUV only in the liver adjacent to the left diaphragmatic dome. CLINICAL RELEVANCE: PPBH was demonstrated to be a feasible PET/CT protocol with higher PET image quality, less organ misalignment on fused PET/CT, and more accurate SUVs of the liver compared to SV PET/CT in healthy dogs.

Can distinction between the renal cortex and outer medulla on ultrasonography predict estimated glomerular filtration rate in canine chronic kidney diseases?

BACKGROUND: Quantitative evaluation of renal cortical echogenicity (RCE) has been tried and developed in human and veterinary medicine. OBJECTIVES: The objective of this study was to propose a method for evaluating RCE quantitatively and intuitively, and to determine associations between ultrasonographic renal structural distinction and estimated glomerular filtration rate (eGFR) in canine chronic kidney disease (CKD). METHODS: Data were collected on 63 dogs, including 27 with normal kidney function and 36 CKD patients. Symmetric dimethylarginine and creatinine concentrations were measured for calculating eGFR. RCE was evaluated as 3 grades on ultrasonography images according to the distinction between the renal cortex and outer medulla. The RCE grade of each kidney was measured. RESULTS: There was a significant difference in eGFR between the group normal and CKD (p < 0.001). As mean of RCE grades (the mean values of each right and left kidney's RCE grade) increases, the proportion of group CKD among the patients in each grade increases (p < 0.001). Also, severity of RCE (classified as "high" if any right or left kidney evaluated as RCE grade 3, "low" otherwise) and eGFR is good indicator for predicting group CKD (p < 0.001). CONCLUSIONS: The degree of distinction between the renal cortex and the outer medulla is closely related to renal function including eGFR and the RCE grade defined in this study can be used as a method of objectively evaluating RCE.

Effects of airway pressure on contrast enhancement and diameter of the pulmonary artery in healthy dogs as determined by use of computed tomography angiography.

OBJECTIVE: To evaluate effects of airway pressure on contrast enhancement and diameter of the pulmonary artery and determine the optimal airway pressure for pulmonary CT angiography in dogs. ANIMALS: 8 healthy Beagles. PROCEDURES: Thoracic CT was performed at end-expiration (0 cm H2O) and 2 positive-pressure end-inspirations (10 and 20 cm H2O). Attenuation curves of enhancement for the sinus of the pulmonary trunk artery were obtained by use of a bolus technique. Contrast medium (300 mg of I/kg) was administered IV, and CT imaging began at the time of peak enhancement. At each pressure, time to peak enhancement, ratio of blood flow from the caudal vena cava to the right side of the heart (KCdVC), and enhancement characteristics and diameter changes of the pulmonary artery were evaluated. RESULTS: All dogs had a significant delay for time to peak enhancement in the sinus of the pulmonary trunk artery as airway pressure increased. The KCdVC progressively increased as airway pressure increased, and there was low contrast enhancement and increased pulmonary artery filling defects at 20 cm H2O. All pulmonary arteries had marked increases in diameter as pressure increased. Arterial distensibility in the gravity-dependent cranial lung region was greater than that in the gravity-independent caudal lung region at the 2 positive-pressure end-inspirations. CONCLUSIONS AND CLINICAL RELEVANCE: Airway pressure affected time to peak enhancement, KCdVC, contrast enhancement, and pulmonary artery diameter. Results suggested that 10 cm H2O could be an optimal pressure for evaluation of the pulmonary artery of dogs by use of CT angiography. (Am J Vet Res 2019;80;756-763).

Esophageal insufflation computed tomography in clinically normal dogs.

OBJECTIVE To assess the feasibility of esophageal insufflation CT (EICT) for evaluation of the esophagus in dogs. ANIMALS 7 clinically normal adult Beagles. PROCEDURES Each dog was anesthetized twice with 1 week between anesthesia sessions. Dogs were positioned in sternal recumbency during all CT scans. During the first anesthesia session, a CT scan was performed before the esophagus was insufflated (insufflation pressure, 0 mm Hg) and unenhanced and contrast-enhanced EICT scans were performed after CO2 was insufflated into the esophageal lumen to achieve a pressure of 5 mm Hg. For the contrast-enhanced scan, each dog received iohexol (600 mg/kg, IV), and the scan was performed 30 seconds later. During the second anesthesia session, unenhanced and contrast-enhanced EICT scans were performed in the same manner except the insufflation pressure achieved was 10 mm Hg. The esophageal luminal cross-sectional area and wall thickness were measured at each of 5 segments, and mean values were compared among the 3 insufflation pressures and between unenhanced and contrast-enhanced images. RESULTS Mean esophageal luminal cross-sectional area increased and esophageal wall thickness decreased as insufflation pressure increased. Measurements did not differ significantly between unenhanced and contrast-enhanced images. The stomach became distended with CO2 at an insufflation pressure of 10 mm Hg but not at 5 mm Hg. No adverse effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested EICT was feasible for esophageal evaluation in dogs. Further research is necessary to determine the optimal insufflation pressure for the procedure and its diagnostic efficacy in diseased patients.

Usefulness of a saline chaser to reduce contrast material dose in abdominal CT of normal dogs.

Use of a saline chaser has been reported to allow reduction of contrast dose and artifacts during computed tomography (CT) examination in humans. This study assesses the extent of contrast dose by using a saline chaser in abdominal CT scans of normal dogs. Five beagles underwent abdominal CT scans. Three protocols were applied: 600 mg I/kg iohexol without saline chaser (protocol 1), 30% lower dose of iohexol (420 mg I/kg) followed by a 10 mL saline chaser (protocol 2), and 40% lower dose of iohexol (360 mg I/kg) followed by a 10 mL saline chaser (protocol 3). Attenuation values were obtained from aorta, portal vein, and liver parenchyma. The maximum enhancement values (MEVs) in protocol 2 were significantly higher than those in protocols 1 and 3 in the aorta; no difference was seen in the portal vein in all protocols. The liver parenchymal MEVs in protocols 1 and 2 were significantly higher than those obtained in protocol 3. In this study, the use of a saline chaser and a reduced dose of contrast material did not affect vessel enhancement. In conclusion, use of a saline chaser for abdominal CT of dogs is recommended because it allows a 30% reduction of contrast dose without decreasing vascular and hepatic parenchymal enhancement.