Kazutaka Yamada

In Vivo SPECT Imaging of Amyloid-β Deposition with Radioiodinated Imidazo[1,2-a]Pyridine Derivative DRM106 in a Mouse Model of Alzheimer's Disease

Noninvasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention for Alzheimers disease (AD). In the present study, we investigated the availability of radiolabeled DRM106 (123/125I-DRM106 [6-iodo-2-[4-(1H-3-pyrazolyl)phenyl]imidazo[1,2-a]pyridine]), a compound with sufficient affinity for the synthesis of human Aβ fibrils and satisfactory metabolic stability, as a SPECT ligand in living brains. Method: The sensitivity of 125I-DRM106 for detecting Aβ deposition was compared with that of 125I-IMPY (2-(4′-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), a well-known amyloid SPECT ligand, by ex vivo autoradiographic analyses in 18-mo-old amyloid precursor protein transgenic mice. To verify the sensitivity and quantitation of radiolabeled DRM106 for in vivo imaging, we compared the detectability of Aβ plaques with 123I-DRM106 and a well-known amyloid PET agent, 11C-labeled Pittsburgh compound B (11C-PiB), in 29-mo-old transgenic mice and age-matched nontransgenic littermates. Additionally, we compared the binding characteristics of 125I-DRM106 with those of 11C-PiB and 11C-PBB3, which selectively bind to Aβ plaques and preferentially to tau aggregates, respectively, in postmortem AD brain sections. Results: Ex vivo autoradiographic analysis showed that measurement with 125I-DRM106 has a higher sensitivity for detecting Aβ accumulation than with 125I-IMPY in transgenic mice. SPECT imaging with 123I-DRM106 also successfully detected Aβ deposition in living aged transgenic mice and showed strong correlation (R = 0.95, P < 0.01) in quantitative analysis for Aβ plaque detection by PET imaging with 11C-PiB, implying that sensitivity and quantitation of SPECT imaging with 123I-DRM106 are almost as good as 11C-PiB PET for the detectability of Aβ deposition. Further, the addition of nonradiolabeled DRM106 fully blocked the binding of 125I-DRM106 and 11C-PiB, but not 11C-PBB3, to AD brain sections, and 125I-DRM106 showed a lower binding ratio of the diffuse plaque–rich lateral temporal cortex to the dense-cored/neuritic plaque–rich hippocampal CA1 area, compared with 11C-PiB. Conclusion: All of these data demonstrated the high potential of 123I-DRM106 for amyloid imaging in preclinical and clinical application, and it might more preferentially detect dense-cored/neuritic amyloid deposition, which is expected to be closely associated with neuropathologic changes of AD.

Computed tomography of the prostate gland in apparently healthy entire dogs

OBJECTIVESnTo describe the computed tomography (CT) features of the prostate gland and determine prostate size using CT in entire male dogs.nnnMETHODSnThe prostate gland was evaluated in 35 dogs. Morphological features including homogeneity, delineation, shape and intraprostatic differentiation were assessed. Height, length, width, area, volume and attenuation values of the prostate gland were measured. Ratios of prostatic height (rH), length and width to the sixth lumbar vertebral body length were calculated. Relationships of prostatic dimensions with body weight and age were evaluated.nnnRESULTSnThe prostate gland was homogeneous in 29 dogs on non-contrast images and 18 of 24 dogs on postcontrast images. Transverse images revealed a semi-oval prostate gland in 29 dogs and irregularly shaped prostate gland in 6 dogs. A prominent median septum was observed in postcontrast images. Significant positive correlations were found between body weight and age and all prostatic dimensions except between age and rH. The mean ± sd values for attenuation were 59·3 ± 9·1 and 121·3 ± 22·7 HU in non-contrast and postcontrast image, respectively.nnnCLINICAL SIGNIFICANCEnCT can be useful for evaluating morphological features of the prostate gland. Prostatic length or width is a better measure than height for computed tomographic estimation of prostate size.

Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-β imaging in Alzheimer's disease.

Non-invasive detection for amyloid-β peptide (Aβ) deposition has important significance for the early diagnosis and medical intervention for Alzheimers disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential imaging agents for single-photon emission computed tomography (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for synthetic human Aβ 1-40 fibrils than did the well-known amyloid-imaging agent IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of (125)I-labeled DRK092 and IMPY; no radioactive metabolites from (125)I-labeled DRM106 ([(125)I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [(125)I]DRM106 in the hippocampal region of AD enriched with Aβ plaques. Thus, our results strongly suggested that compound DRM106 can be used as an imaging agent for SPECT to detect Aβ deposition in AD brain.

Extracranial meningioma in a dairy cow

MENINGIOMA is one of the most common primary intracranial tumours in cats and dogs, but is rarely reported in cattle (Koestner and Higgins 2002). The meningiomas that have been found in cattle have been primary intracranial tumours (Bwangamoi and Sachs 1969, Yadgirker and others 1970, Josephson and Little 1990). There are six recognised histological types of meningiomas: meningiothelial, transitional, angioblastic, microcystic, psammomatous and fibroblastic (Koestner and Higgins 2002). All previously reported cases of bovine meningioma have been fibroblastic, except for one which was psammomatous (Eroksuz and others 1999). Koestner and Higgins (2002) reported that in dogs, 82 per cent of all meningiomas are intracranial, 15 per cent are intraspinal and 3 per cent are retrobulbar. Even in human beings, who have a comparatively high rate of meningioma, extracranial meningioma is a very rare presentation (Trotter and others 2001, Nadkarni and others 2002). This short communication describes a case of extracranial meningioma in a dairy cow. A five-year-old Holstein cow was admitted to the Veterinary Medical Teaching Hospital of Obihiro University. The cow presented with a non-painful swelling on the right side of the forehead and exophthalmos of the right eye (Fig 1), which was reported as having been progressively worsening over a period of nine months. Despite this condition, the cow had been eating well, appeared healthy and showed no neurological signs. Before admission, chronic frontal sinusitis had been tentatively diagnosed and a treatment of antibiotics prescribed; however, the treatment was unsuccessful and the cow’s deformity continued to worsen. On admission, the cow’s rectal temperature, heart rate, respiratory rate and the results of haematological examination were all within reference ranges. Blood chemistry revealed an elevated level of lactate dehydrogenase (2330 iu/l, reference range 1700 to 2300 iu/l); the levels of alkaline/phosphatase, calcium and phosphorus appeared normal. Radiographs of the skull revealed a soft tissue opacity at the right aspect of the frontal bone, parietal bone and frontal sinus. Signs of fluid were not observed. The initial differential diagnosis of the abnormal head conformation was chronic frontal sinusitis, abscess, osteoma or malignant neoplasia. However, the haematological examination and radiographs did not indicate an infection. The decision was therefore made to trephine the forehead over the mass. This revealed no fluid or abscess, but a solid, yellowish-white mass was found in the frontal sinus. Histopathological examination of a biopsy specimen revealed a neoplastic proliferation of spindle cells arranged in interfacing fascicles; storiform patterns and whorl formations were also seen. The neoplastic cells within the mass had basophilic, ovoid or polygonal nuclei with dispersed chromatin, and mitotic figures were frequently observed. The spindle cells were separated by mild to moderate amounts of collagen. Multifocal areas of necrosis and calcification were observed. The tumour cells did not appear to invade the vessels. On the basis of these findings, a fibroblastic tumour or meningioma was suspected, but the origin of the tumour could not be identified. The animal was euthanased at the owner’s request. Before gross dissection, the cow’s head was examined using computed tomography (CT) and magnetic resonance imaging (MRI), with the purpose of establishing the internal anatomy of the lesion. Images were obtained with a helical

Quantitative evaluation of cervical cord compression by computed tomographic myelography in Thoroughbred foals

ABSTRACT Five Thoroughbred foals (age, 8–33 weeks; median age, 31 weeks; weight, 122–270 kg; median weight, 249 kg) exhibiting ataxia with suspected cervical myelopathy (n=4) and limb malformation (n=1) were subjected to computed tomographic (CT) myelography. The areas of the subarachnoid space and cervical cord were measured on transverse CT images. The area of the cervical cord was divided by the area of subarachnoid space, and stenosis ratios were quantitatively evaluated and compared on the basis of histopathological examination. The sites with a ratio above 52.8% could have been primary lesion sites in the histopathological examination, although one site with a ratio of 54.1% was not a primary lesion site. Therefore, in this study, a ratio between 52.8–54.1% was suggested to be borderline for physical compression that damages the cervical cord. All the cervical vertebrae could not be scanned in three of the five cases. Therefore, CT myelography is not a suitable method for locating the site of compression, but it should be used for quantitative evaluation of cervical stenosis diagnosed by conventional myelography. In conclusion, the stenosis ratios determined using CT myelography could be applicable for detecting primary lesion sites in the cervical cord.

Mobility of the forearm in the raccoon (Procyon lotor), raccoon dog (Nyctereutes procyonoides) and red panda (Ailurus fulgens).

The ranges of pronation/supination of forearms in raccoons, raccoon dogs and red pandas were nondestructively examined. Three carcasses of each species were used for CT analysis, and the left forearms were scanned with a CT scanner in two positions: maximal supination and maximal pronation. Scanning data were reconstructed into three-dimensional images, cross-sectional images were extracted at the position that shows the largest area in the distal part of ulna, and then, the centroids of each cross section of the radius and ulna were detected. CT images of two positions were superimposed, by overlapping the outlines of each ulna, and then, the centroids were connected by lines to measure the angle of rotation, as an index of range of mobility. The measurements in each animal were analyzed, using the Tukey–Kramer method. The average angle of rotation was largest in raccoons and smallest in raccoon dogs, and the difference was significant. In the maximally pronated forearm of all species, the posture was almost equal to the usual grounding position with palms touching the ground. Therefore, the present results demonstrate that the forearms of raccoons can supinate to a greater degree from the grounding position with palms on the ground, as compared with those of raccoon dogs and red pandas.

Use of a saline chaser to reduce the dose of contrast material for dynamic CT in cattle.

To investigate the effectiveness of a saline chaser in reducing the required dose of contrast material while carrying out dynamic CT scans in cattle, six clinically normal Holstein calves were subjected to CT scans of the head in a study using a crossover design. The calves were studied as three groups: group A received only contrast material (600 mgI/kg); group B received a 30 per cent lower dose of the same contrast material followed by 50 ml of saline solution; and group C received a 40 per cent lower dose of the same contrast material followed by 50 ml of saline solution. In all the animals, a power injector was used for administering the contrast material, with an injection rate of 4 ml/s and a pressure of 4.7 to 5.7 kg/cm2. Attenuation values were obtained from the right and left maxillary arteries and dorsal sagittal sinus. There were no significant differences in the maximum enhancement value (MEV) of the maxillary arteries and dorsal sagittal sinus between groups A and B. The MEVs of the maxillary arteries and dorsal sagittal sinus in groups A and B were significantly greater than the MEV in group C (P<0.05). The use of a saline chaser allowed a 30 per cent reduction in the dose of contrast material without decreasing vascular enhancement.

Displacement of the large colon in a horse with enterolithiasis due to changed positions observed by computed tomography

ABSTRACT Computed tomography (CT) was performed for an 18-year-old female pony with enterolithiasis in the prone and supine positions. CT images from the prone position revealed displacement of the large dorsal colon, which contained an enterolith to the ventral side of the abdomen, and those from the supine position revealed displacement to the dorsal side. A high-density material suggestive of a metallic foreign body was also observed in the enterolith core. An enterolith (422 g, 104 mm) was surgically removed from the large dorsal colon. This caused no complications after surgery and increased the horse’s weight. Changing positions during CT helps identify the exact location of enterolith and intestinal displacement due to enterolith weight, as well as size and number.

Fluoroscopic observation of the development of displaced abomasum in dairy cows

To clarify the mechanisms underlying the development of displaced abomasum (DA), we repositioned DA in 12 cows by rolling and observed the course of redisplacement using X-ray fluoroscopy. Displacement of the abomasum was observed to follow three patterns: displacement to the left side of the abdominal cavity through the gap formed at the reticulum, atrium of the rumen and ventral sac of the rumen (n=7); displacement to the left side after cranial movement along the diaphragm (n=3); displacement to the right side after cranial movement along the diaphragm (n=2). These differences were considered to be associated with the rumen volume. To the best of our knowledge, this is the first study reporting the visual observation of the course of DA in dairy cows.

Signal changes in standing magnetic resonance imaging of osseous injury at the origin of the suspensory ligament in four Thoroughbred racehorses under tiludronic acid treatment

ABSTRACT Problems associated with the proximal metacarpal region, such as an osseous injury associated with tearing of Sharpey’s fibers or an avulsion fracture of the origin of the suspensory ligament (OISL), are important causes of lameness in racehorses. In the present study, four Thoroughbred racehorses (age range, 2–4 years) were diagnosed as having forelimb OISL and assessed over time by using standing magnetic resonance imaging (sMRI). At the first sMRI examination, all horses had 3 characteristic findings, including low signal intensity within the trabecular bone of the third metacarpus on T1-weighted images, intermediate-to-high signal intensity surrounded by a hypointense rim on T2*-weighted images, and high signal intensity on fat-suppressed images. Following the sMRI examination, all horses received 50 mg of tiludronic acid by intravenous regional limb perfusion once weekly for 3 weeks. Attenuation of the high signal intensity on T2*-weighted and fat-suppressed images was observed on follow-up sMRI in 3 horses. Following rest and rehabilitation, these 3 horses successfully returned to racing. In contrast, the other horse that did not show attenuation of the high signal intensity failed to return to racing. To our knowledge, this is the first report of OISL in Thoroughbred racehorses assessed over time by sMRI under tiludronic acid treatment. Our findings support the use of sMRI for examining lameness originating from the proximal metacarpal region to refine the timing of returning to exercise based on follow-up examinations during the recuperation period.