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Biomedical subjects

Motohiro Kiyosawa

Publications and source records attributed to Motohiro Kiyosawa.

At least 19 recordsLinked to original sources

Differential activation of cerebral blood flow by stimulating amblyopic and fellow eye.

PURPOSE: Positron emission tomography (PET), the blood flow response in the primary visual cortex (V1) to two visual stimuli, low temporal frequency (6 Hz) to activate the parvocellular system, and high temporal frequency (25 Hz) to activate the magnocellular system were used to investigate pathophysiologic mechanism of amblyopia. METHODS: Five women and one man who were aged between 26 and 60 years, who were ophthalmologically normal except for amblyopia, and who had corrected visual acuity in the amblyopic eye of 0.6 or worse were examined. An intravenous injection of the H(2)(15)O was given, and the regional cerebral blood flow was measured by PET during full-field stimulation with either 6 Hz or 25 Hz flicker to the amblyopic or the sound eye. RESULT: The activation of blood flow in the contra-lateral area V1 by the 6-Hz stimulation of the sound eye was greater than that during the stimulation of the amblyopic eye (P<0.05, small volume correction, n=6). With 25-Hz stimulation of the sound and amblyopic eyes, the blood flow in the contra-lateral and ipsi-lateral areas V1 was not significantly different. CONCLUSION: The decreased activation of blood flow in the contra-lateral V1 by low temporal frequency stimuli supports the hypothesis that the parvocellular pathway in amblyopic eyes is depressed.

Adult↗

PRBS-determined temporal frequency characteristics of VEP in glaucoma.

The purpose of this study was to determine whether the PRBS-VEP-determined temporal frequency characteristics (TFCs) of the visual pathways are useful for evaluating the properties of the visual system of glaucomatous patients. The VEPs elicited by pseudorandom stimulation (PRBS) with red LEDs were recorded from 26 eyes with primary open angle glaucoma and 11 age-matched normal eyes. The glaucomatous patients were divided into 3 groups according to the size and shape of their visual field defect; early (9), moderate (9), and severe (8). The cross-spectrum between the PRBS and PRBS-VEPs was used as the TFCs. The TFC of each glaucomatous group were compared to those of the normal controls. A depression of the TFC was found for the middle and high frequencies (18-28 Hz) in the moderate group, and the depression spread to lower frequencies (4-16 Hz) in the severe groups. The TFC values at 14-20 Hz were depressed in the moderate group and most frequencies were depressed significantly with the progression of glaucoma (p < 0.05). The sensitivity of the TFC at 18-20 Hz was 56%, 89% and 100% in the early, moderate and severe glaucoma groups, respectively, and the specificity was 82%. We conclude that the PRBS-determined TFC is altered in glaucomatous eyes, and the frequencies depressed were related to the degree of glaucoma. These findings indicate that the PRBS-determined TFC can be useful for evaluating visual function of glaucomatous eyes.

Aged↗

Characteristics of first and second order kernels of visually evoked potentials elicited by pseudorandom stimulation.

The characteristics of the first and the second order kernels of the visually evoked potentials (VEPs) elicited by pseudorandom binary sequence (PRBS) stimuli were investigated. VEPs were recorded from six eyes of four normal volunteers. The effects of stimulus luminance on the latency and amplitude of the first and the second order kernels were determined. The temporal interactions of transient VEPs elicited by single and double pulse stimuli were compared with the first and the second order kernels of the PRBS-VEPs. The correlation coefficient between the logarithm of the stimuli luminance (log I) and VEP amplitude of the first order kernels was 0.45 (p < 0.05), and that between log I and P1 latency was -0.62 (p < 0.005). The second order kernels were not equal to the temporal interactions of the responses. However, the latency of the negative peak of the fourth slice was similar to the temporal interaction to double pulse stimulation with an inter-stimulus interval of 40 ms. An inhibitory component at 40 ms following the first stimulus was detected in the analysis of both PRBS-VEPs second order kernel and transient VEPs. This function may help to increase the frequency of critical flicker fusion in normal subjects.

Adult↗

Glucose hypometabolism in medial frontal cortex of patients with apraxia of lid opening.

PURPOSE: To determine whether regional cerebral functional abnormalities exist in patients with apraxia of lid opening (ALO). METHODS: Cerebral glucose metabolism was examined by positron emission tomography (PET) in 11 patients (8 women and 3 men, age 48-69 years); 10 with ALO accompanied by blepharospasm and 1 patient with pure ALO. Eleven normal volunteers (6 women and 5 men, age 45-66 years) were examined as controls. A comprehensive ophthalmological examination, magnetic resonance imaging (MRI), and PET were performed. The cerebral glucose metabolism was evaluated by the relative uptake of [fluorine-18]fluorodeoxyglucose by PET. The mean +/- two standard deviations of the normal controls was defined as the normal range for cerebral glucose metabolism. RESULTS: MRI revealed no particular lesion except for an infarction in the unilateral basal ganglia in two patients. Decreased glucose metabolism was observed in a wide area of the medial frontal lobe (six cases) and primary visual cortex (PVC) (four cases). Group multiple comparisons revealed a significant decrease ( P<0.0035) in the bilateral anterior cingulate gyrus, left supplementary motor area (SMA), and bilateral PVC. CONCLUSION: The results support the hypothesis that ALO is associated with hypofunction in the SMA and/or anterior cingulate gyrus.

Aged↗

Increased regional cerebral blood flow but normal distribution of GABAA receptor in the visual cortex of subjects with early-onset blindness.

Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [(15)O]water and [(11)C]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development.

Adult↗

Correlation between frequency doubling technology perimetry and temporal frequency characteristics in early glaucoma.

To assess the effectiveness of the temporal frequency characteristics (TFC) as an indicator of visual damage in patients with early open-angle glaucoma, TFC obtained from VEPs elicited by a pseudorandom binary sequence (PRBS) stimulus was compared with the frequency doubling technology (FDT) thresholds. Cross power spectrum between the PRBS stimulus as the input and the PRBS-VEPs as the output was calculated, and was used as the TFC. The normalized amplitude of the TFC at 2-4, 6-8, 10-12, 14-16, 18-20, 22-24, 26-28, and 30-32 Hz was calculated, and a coefficient of correlation between these values and the FDT thresholds was determined. The coefficients of correlation between the FDT thresholds and the TFC at 18-20 Hz for the central, 10 degrees, 20 degrees, and 30 degrees were r = 0.03, 0.31, 0.21, and 0.16, respectively in non-glaucomatous normal control eyes, and those for the same regions of eyes with early glaucoma were r = 0.66, 0.46, 0.38, and 0.35, respectively. The coefficients of correlation between the FDT thresholds and TFC at temporal frequencies were relatively high at 18-20 and 26-32 Hz. The time required to obtain the PRBS-VEP data was approximately the same as that for the FDT thresholds. The strong correlation between the two tests indicates that the FDT values and the high temporal frequency segments of the TFC may be useful as a preliminary indicator of visual damage in patients with early open-angle glaucoma. In addition, the strong correlation suggests that there was a preferential damage to the magnocellular system in glaucomatous eyes.

Aged↗

Quantitative in vivo measurement of central benzodiazepine receptors in the brain of cats by use of positron-emission tomography and [11C]flumazenil.

OBJECTIVE: To map central benzodiazepine receptors (BZRs) in the brain of cats by use of positron-emission tomography (PET) and [11C]flumazenil. ANIMALS: 6 male cats that weighed between 2.0 and 3.6 kg. PROCEDURE: Brain images obtained by PET evaluation of [11C]flumazenil were superimposed on T2-weighted magnetic-resonance imaging (MRI) scans of the same cats. Detailed anatomic regions, such as the cerebral cortex, striatum, thalamus, midbrain, and cerebellum, on the PET images were evident by PET-MRI registration. Regional binding of [11C]flumazenil to BZRs was quantitatively measured by use of a model with 2 tissue compartments and 4 variables. RESULTS: The highest value for distribution volume was observed in the cerebral cortex, and the lowest value was found in the midbrain of cats. CONCLUSIONS AND CLINICAL RELEVANCE: Binding of [11C]flumazenil to BZRs in the brain of cats can be quantitatively measured by use of PET with the aid of PET-MRI registration. It is difficult to diagnose changes in these neuroreceptors within the field of current veterinary science. In the future, PET should prove useful for investigating and diagnosing brain disorders in animals in clinical settings.

Animals↗

Detection of visual activation of lateral geniculate nucleus by positron emission tomography.

PURPOSE: Although activation of the lateral geniculate nucleus (LGN) has been shown by functional magnetic resonance imaging, a quantitative evaluation of the activity has not been reported by positron emission tomography (PET). The purpose of this study was to quantify the degree of activation of the LGN and other vision-related structures by visual stimuli as detected by PET. METHODS: PET activation was induced by a bolus injection of 15O-labelled water (H2(15)O) in six normal volunteers. The regional cerebral blood flow (rCBF) was measured under three conditions: eyes closed, binocular flickering light stimulation, and binocular viewing of a video movie. Single-subject analysis, group analysis, and correlation analysis were performed. RESULTS: Although single-subject analysis did not show significant changes, group analysis revealed a significant increase in rCBF in the left LGN induced by flickering light stimulation ( P<0.01) and video stimulation ( P<0.05). Localization of the activation foci in the LGN agreed with the retinotopic organization of the LGN. CONCLUSION: Although the LGN is relatively small compared with the resolution of the PET image, visually activated blood flow changes could be determined by H2(15)O PET:

Adult↗

Visualization of sigma1 receptors in eyes by ex vivo autoradiography and in vivo positron emission tomography.

Sigma receptors are present on the neurons of the central nervous system and in peripheral organs. They have also been demonstrated in ocular tissues by in vitro membrane binding assays. We have investigated whether sigma(1) receptors can be demonstrated in rat eyes by ex vivo autoradiography using [(11)C]SA4503, a selective radioligand. We also tested whether in vivo positron emission tomography (PET) can be used to show sigma(1) receptors in rabbit eyes. In rats, a high accumulation of [(11)C]SA4503 was found in the iris-ciliary body and retina. A carrier-loading experiment showed that the receptor-specific binding of [(11)C]SA4503 was approximately 75% of the total binding in the brain. Sigma(1) receptors were also detected in the projecting terminals of the retina to the superior colliculus. PET showed radioactivity in the anterior segment including the iris-ciliary body and retina, and pretreatment or displacement by a sigma receptor ligand (haloperidol), suggested that the PET signal reflects radioligand-receptor binding. The high density of sigma(1) receptors in the iris-ciliary body and retina was confirmed by ex vivo autoradiography. In conclusion, the iris-ciliary body and retina are rich in sigma(1) receptors, and PET may be used to investigate the in vivo distribution of these neuroreceptors in the eye.

Animals↗

Mapping adenosine A(1) receptors in the cat brain by positron emission tomography with [(11)C]MPDX.

We evaluated the potential of [(11)C]MPDX as a radioligand for mapping adenosine A(1) receptors in comparison with previously proposed [(11)C]KF15372 in cat brain by PET. Two tracers showed the same brain distribution. Brain uptake of [(11)C]MPDX (Ki = 4.2 nM) was much higher and washed out faster than that of [(11)C]KF15372 (Ki = 3.0 nM), and was blocked by carrier-loading or displaced with an A(1) antagonist. The regional A(1) receptor distribution evaluated with kinetic analysis is consistent with that previously measured in vitro. [(11)C]MPDX PET has a potential for mapping adenosine A(1) receptors in brain.

Animals↗

Microdissection and gene rearrangement analysis of paraffin-embedded specimens of orbital malignant lymphoma.

PURPOSE: To determine whether a definite diagnosis of malignant lymphoma can be made from paraffin-embedded archived orbital specimens by gene rearrangement analysis using microdissection and polymerase chain reaction (PCR). METHODS: Specimens from four patients with histopathologically diagnosed orbital malignant lymphoma were examined. The malignant cells were microdissected off the paraffin-embedded specimens. DNA was extracted from the cells, and the immunoglobulin heavy chain ( IgH) gene was amplified by PCR. Gene rearrangements were detected by using primers for the third framework (FR3A), the second framework (FR2A), and the complementary determining region 3 (CDR3). Translocation of the B-cell lymphoma/leukemia-2 ( bcl-2) gene was also examined. RESULTS: Malignant cells were present on the slides of the paraffin-embedded specimens of three of four cases. The specimens from these three cases showed IgH rearrangements for FR3A, FR2A, and CDR3. A bcl-2-associated translocation was also detected in one case. CONCLUSIONS: Gene rearrangement analysis is applicable to paraffin-embedded archived orbital specimens to confirm a diagnosis of malignant lymphoma. The advantage of this method is that only a small specimen is needed because the detection sensitivity is high.

Complementarity Determining Regions↗

Oscillopsia associated with dysfunction of visual cortex.

PURPOSE: To investigate the cause of oscillopsia without nystagmus or vestibular dysfunction in a 31-year-old man with no past history of serious illness. METHODS: The changes in the regional cerebral blood flow elicited by visual stimuli were studied by positron emission tomography (PET) in the patient and were compared with changes in normal subjects. The primary visual cortex (PVC) and area V5 were defined on Talairach coordinates, as shown in previous PET studies, and were confirmed with their activation patterns in our subjects. RESULTS: Flicker stimulation (8 Hz) and a stationary random dot pattern activated area V5 in the patient, but not in the six normal controls. A moving random dot pattern activated both the PVC and the extra-striate cortex in both the patient and the controls. CONCLUSIONS: Oscillopsia in this case is associated with dysfunction of the visual cortices and may be caused by it.

Adult↗

A case of multiple sclerosis with homonymous hemianopia examined by positron emission tomography.

BACKGROUND: To demonstrate the efficacy of positron emission tomography (PET) for examining multiple sclerosis (MS) patients with hemianopia. CASE: A 20-year-old man visited us with a complaint of left homonymous hemianopia and headache. OBSERVATIONS: The patient's visual acuity was 1.2 (n.c.) OD and 0.9 (1.0) OS. Magnetic resonance imaging (MRI) showed a mass in the temporoparietal lobe. A pathological diagnosis of MS was made by brain biopsy. Low glucose metabolism in the lesion and visual cortex was observed by PET with (18)F-fluorodeoxy glucose. PET with (11)C-flumazenyl revealed a reduction of (11)C-uptake in the demyelinated optic radiation, and only a slight reduction of (11)C-uptake in the primary visual cortex. The results of (11)C-flumazenyl PET suggested a slight reduction of neuronal density. In 2 years, the visual field recovered to the normal state. CONCLUSION: PET can be a useful tool for estimating the visual outcome of patients with hemianopia in MS.

Adult↗

Glucose metabolism in the visual structures of rat monocularly deprived by eyelid suture after postnatal eye opening.

PURPOSE: To determine the changes in the visual centers of rats following monocular visual deprivation after postnatal eyelid opening (PEO). METHODS: Monocular eyelid suture was performed on rats on days 1, 3, 5, 7, 14, and 28 after PEO, and the glucose metabolism was measured 1, 2, 5, and 7 days after the eyelid suture. Ex vivo autoradiography with (14)C- or (18)F-labeled 2-deoxy-D-glucose was carried out. Effects of monocular enucleation or dark rearing were also determined. RESULTS: Monocular eyelid suture did not decrease the glucose metabolism in any contralateral visual structures on day 1 after visual deprivation in the PEO1 or PEO3 lid-sutured rats. However, there was a decrease on day 1 after the eyelid suture in PEO7 and older rats. Similarly, monocular enucleation on PEO1 did not reduce the glucose metabolism in the visual cortex (VC), but enucleation on PEO7 and thereafter did. Eyelid suture on PEO8 following dark rearing until PEO7 did not reduce the glucose metabolism 1 day after suture, but reduced it at 7 days after suture. CONCLUSIONS: Glucose metabolism was altered by visual deprivation on PEO7 and thereafter. Five days of visual experience after PEO were required for initiation of visual function in the rat visual system.

Animals↗

Visual evoked potentials elicited by pseudorandom stimulation from patients with macular degeneration.

PURPOSE: To investigate the effect of a central scotoma on the amplitude, implicit time (IT), and temporal frequency characteristics (TFC) of the visual evoked potentials (VEPs) elicited by a pseudorandom binary sequence (PRBS) stimulus in age-related macular degeneration (AMD) patients. METHODS: Twenty-six patients with AMD, 17 eyes with visual acuity of less than 20/100, and 9 eyes with visual acuity between 20/70 and 20/25, were examined. Nine eyes of age-matched healthy volunteers served as controls. To elicit the PRBS-VEPs, one eye was stimulated with a PRBS stimulus. The first-order kernel was calculated from a cross-correlation between the PRBS and the VEPs. The Fourier transformed first-order kernel was used as the TFC of the visual system. RESULTS: The mean IT of P2 (second positive peak) of the first-order kernel was significantly delayed (t-test, P <.05), and the P2-N2 (peak-to-peak of P2 and second negative peak N2) amplitude was significantly reduced (t-test, P <.01) in eyes with AMD. A depression of the TFC values in the 6-18 Hz band was prominent in patients with AMD (t-test, P <.01). CONCLUSION: PRBS-VEPs demonstrated a prolonged IT and reduced amplitude of the first-order kernel, and reduced TFC with a reduction of visual acuity in patients with macular degeneration.

Aged↗

Neuroimaging analysis of a case with left homonymous hemianopia and left hemispatial neglect.

PURPOSE: To correlate the neuro-ophthalmological observations with the magnetic resonance images (MRI) and positron emission tomographic (PET) findings in a case with left homonymous hemianopia and left hemispatial neglect. CASE: A 57-year-old woman underwent surgery for a ruptured anterior communicating artery aneurysm. After she recovered consciousness, it was found that she had left homonymous hemianopia and left hemispatial neglect. Although the hemispatial neglect slowly improved, the homonymous hemianopia persisted. MRI and measurements of cerebral glucose metabolism by 2-fluoro-2-deoxy-D-glucose(FDG)-PET were performed 1 year later. RESULTS: MRI revealed infarctions on the medial surface of the frontal lobe, on the right medial surface of the occipital lobe, and global atrophy of the right cortical hemisphere. FDG-PET disclosed severe glucose hypometabolism in the entire right hemisphere. Glucose metabolism in the right occipital cortex was 61.1% of that in the homologous region on the left side, 62.8% in the right anterior cingulate gyrus, and 93.8% in the temporal-parietal-occipital junction. CONCLUSIONS: The low glucose metabolism in the right visual cortex explains the persistent left hemianopia, and that in the right anterior cingulate gyrus and the right temporal-parietal-occipital junction may be responsible for the left hemispatial neglect. The relatively mild damage in the right temporal-parietal-occipital junction explained the recovery of the neglect symptom. Measurements of regional cerebral glucose metabolism by PET are useful for determining the cause of cerebral visual dysfunction and its prognosis after a cerebral lesion.

Aneurysm, Ruptured↗

Clinical findings in Japanese patients with Waardenburg syndrome type 2.

PURPOSE: To determine the visual characteristics of Japanese subjects with the Waardenburg syndrome type 2. METHODS: The visual functions of 11 albino patients who were identified from the screening of 240 children attending a school for children with a hearing deficit were studied. The ophthalmological examinations included eye position, visual acuity, biomicroscopy, ophthalmoscopy, visual field by confrontation or Goldmann's perimetry, stereoacuity by the Titmus test, and color vision by the Ishihara pseudoisochromatic plates. RESULTS: A combination of congenital sensory deafness and partial ocular albinism without lateral displacement of the lacrimal puncta was observed in 11 (4.6%) of the students with hearing deficit. All these children had sectorial heterochromia irides with local retinal hypopigmentation. Lid deformities were not present. The retinal vasculature was normal, and macular hypoplasty was not found. Other than 1 eye with hyperopic amblyopia, no serious visual disturbance was found in these patients. CONCLUSIONS: The 11 students were classified as having Waardenburg syndrome type 2. None had a critical visual deficit, and all had partial heterochromia irides and retinal hypopigmentation.

Adolescent↗