Mikio Hiura

Changes in cerebral blood flow during steady-state cycling exercise: a study using oxygen-15-labeled water with PET

Cerebral blood flow (CBF) during dynamic exercise has never been examined quantitatively using positron emission tomography (PET). This study investigated changes in CBF that occur over the course of a moderate, steady-state cycling exercise. Global and regional CBF (gCBF and rCBF, respectively) were measured using oxygen-15-labeled water (H215O) and PET in 10 healthy human subjects at rest (Rest), at the onset of exercise (Ex1) and at a later phase in the exercise (Ex2). At Ex1, gCBF was significantly (P<0.01) higher (27.9%) than at Rest, and rCBF was significantly higher than at Rest in the sensorimotor cortex for the bilateral legs (M1Leg and S1Leg), supplementary motor area (SMA), cerebellar vermis, cerebellar hemispheres, and left insular cortex, with relative increases ranging from 37.6% to 70.5%. At Ex2, gCBF did not differ from Rest, and rCBF was significantly higher (25.9% to 39.7%) than at Rest in only the M1Leg, S1Leg, and vermis. The areas showing increased rCBF at Ex1 were consistent with the central command network and the anatomic pathway for interoceptive stimuli. Our results suggest that CBF increases at Ex1 in parallel with cardiovascular responses then recovers to the resting level as the steady-state exercise continues.

Initial Human PET Studies of Metabotropic Glutamate Receptor Type 1 Ligand 11C-ITMM

N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-11C-methoxy-N-methylbenzamide (11C-ITMM) is a potential radioligand for mapping metabotropic glutamate receptor type 1 (mGluR1) in the brain by PET. The present study was performed to determine the safety, distribution, radiation dosimetry, and initial brain imaging of 11C-ITMM in healthy human subjects. Methods: The multiorgan biodistribution and radiation dosimetry of 11C-ITMM were assessed in 3 healthy human subjects, who underwent 2-h whole-body PET scans. Radiation dosimetry was estimated from the normalized number of disintegrations of source organs using the OLINDA/EXM program. Five healthy human subjects underwent 90-min dynamic 11C-ITMM scans of brain regions with arterial blood sampling. For anatomic coregistration, T1-weighted MR imaging was performed. Metabolites in plasma and urine samples were analyzed by high-performance liquid chromatography. 11C-ITMM uptake was assessed quantitatively using a 2-tissue-compartment model. Results: There were no serious adverse events in any of the subjects throughout the study period. 11C-ITMM PET demonstrated high uptake in the urinary bladder and gallbladder, indicating both urinary and fecal excretion of radioactivity. The absorbed dose (μGy/MBq) was highest in the urinary bladder wall (13.2 ± 3.5), small intestine (9.8 ± 1.7), and liver (9.1 ± 2.0). The estimated effective dose for 11C-ITMM was 4.6 ± 0.3 μSv/MBq. 11C-ITMM showed a gradual increase of radioactivity in the cerebellar cortex. The total distribution volume in the brain regions ranged from 2.61 ± 0.30 (cerebellar cortex) to 0.52 ± 0.17 (pons), and the rank order of the corresponding total distribution volume of 11C-ITMM was cerebellar cortex > thalamus > frontal cortex > striatum ≈ pons, which was consistent with the known distribution of mGluR1 in the primate brain. The rate of 11C-ITMM metabolism in plasma was moderate: at 60 min after injection, 62.2% ± 8.2% of the radioactivity in plasma was intact parent compound. Conclusion: The initial findings of the present study indicated that 11C-ITMM PET is feasible for imaging of mGluR1 in the brain. The low effective dose will permit serial examinations in the same subjects.

Cerebral Oxygenation in the Frontal Lobe Cortex during Incremental Exercise Tests: The Regional Changes Influenced by Volitional Exhaustion

The present study examined the regional differences of cortical oxygenation in the frontal lobe by near-infrared spectroscopy (NIRS) during incremental exercise tests and the precise location of NIRS was examined by brain magnetic resonance imaging (MRI). Pulmonary gas exchange and NIRS measurement during incremental cycling ergometry tests were investigated in 14 men. In 7 of these subjects, the right middle cerebral artery mean velocity (MCA Vmean) was simultaneously measured by transcranial Doppler (TCD). In the right medial of the frontal lobe cortex, Tissue Oxygenation Index (TOI) increased by 8.8% with its peak value at respiratory compensation threshold (RCT) and Normalized Tissue Hemoglobin Index (nTHI) increased until endpoint by 16.2%. During incremental exercise tests, the changing pattern of TOI was different according to the distribution of the probes. Volitional exhaustion by exercise induced the deteriorated TOI and MCA Vmean, whereas nTHI increased.

Test-retest variability of adenosine A2A binding in the human brain with 11C-TMSX and PET

BackgroundThe goal of the present study was to evaluate the reproducibility of cerebral adenosine A2A receptor (A2AR) quantification using 11C-TMSX and PET in a test-retest study.MethodsFive healthy volunteers were studied twice. The test-retest variability was assessed for distribution volume (VT) and binding potential relative to non-displaceable uptake (BPND) based on either metabolite-corrected arterial blood sampling or a reference region. The cerebral cortex and centrum semiovale were used as candidate reference regions.ResultsTest-retest variability of VT was good in all regions (6% to 13%). In the putamen, BPND using the centrum semiovale displayed a lower test-retest variability (3%) than that of BPND using the cerebral cortex as a reference region (5%). The noninvasive method showed a higher or similar level of test-retest reproducibility compared to the invasive method.ConclusionsBinding reproducibility is sufficient to use 11C-TMSX as a tool to measure the change in A2AR in the human brain.

PET Molecular Imaging to Investigate Higher Brain Dysfunction in Patients with Neurotrauma

INTRODUCTION Many neurotrauma patients suffer from higher brain dysfunction even when focal brain damage is not detected with MRI. We performed functional imaging with positron emission tomography (PET) to clarify the relationship between the functional deficit and symptoms of such patients. METHODS Patients who complain of higher brain dysfunction without apparent morphological cortical damage were recruited. Thirteen patients underwent PET study to image glucose metabolism by (18)F-FDG, and central benzodiazepine receptor (cBZD-R) by (11)C-flumazenil, together with measurement of cognition. RESULTS Diffuse axonal injury (DAI) patients have a significant decrease in glucose metabolism and cBZD-R distribution in the cingulated cortex than normal controls. Score of cognition test was variable among patients. The degree of decreased glucose metabolism and cBZD-R in the dominant hemisphere corresponded well to the severity of cognitive disturbance. Patients with a milder type of diffuse brain injury (i.e., cerebral concussion) also showed abnormal glucose metabolism and cBZD-R distribution when they suffered from cognitive deficit. CONCLUSION PET molecular imaging was useful for depicting the cortical dysfunction of neurotrauma patients even when morphological change was not apparent. This method may be promising in clarifying the pathophysiology of higher brain dysfunction of patients with neurotrauma, but without morphological abnormality.

Response of Cerebral Blood Flow and Blood Pressure to Dynamic Exercise: A Study Using PET

Dynamic exercise elicits fluctuations in blood pressure (BP) and cerebral blood flow (CBF). This study investigated responses in BP and CBF during cycling exercise and post-exercise hypotension (PEH) using positron emission tomography (PET). CBF was measured using oxygen-15-labeled water (H215O) and PET in 11 human subjects at rest (Rest), at the onset of exercise (Ex1), later in the exercise (Ex2), and during PEH. Global CBF significantly increased by 13% at Ex1 compared with Rest, but was unchanged at Ex2 and during PEH. Compared with at Rest, regional CBF (rCBF) increased at Ex1 (20~42%) in the cerebellar vermis, sensorimotor cortex for the bilateral legs (M1Leg and S1Leg), insular cortex and brain stem, but increased at Ex2 (28~31%) only in the vermis and M1Leg and S1Leg. During PEH, rCBF decreased compared with Rest (8~13%) in the cerebellum, temporal gyrus, piriform lobe, thalamus and pons. The areas showing correlations between rCBF and mean BP during exercise and PEH were consistent with the central autonomic network, including the brain stem, cerebellum, and hypothalamus (R2=0.25-0.64). The present study suggests that higher brain regions are coordinated through reflex centers in the brain stem in order to regulate the cardiovascular response to exercise.

Contribution of aerobic and anaerobic capacity to 2000 m rowing performance

Background Previous studies strongly have supported importance of aerobic capacity for 2000m rowing performance [1-3] and there are few studies that demonstrated anaerobic capacity had critical role in rowing performance [4-6]. The purpose of the present study is to investigate the relationship between 2000m rowing performance and anaerobic capacity, which were estimated by critical power (CP) model [7,8] and by all-out tests of short duration as well. We also examined aerobic capacity.

Memory deficits due to brain injury: unique PET findings and dream alterations

The authors herein report the case of a young male with memory deficits due to a traumatic head injury, who presented with sleep-related symptoms such as hypersomnia and dream alterations. Although MRI and polysomnography showed no abnormalities, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and 11C flumazenil (FMZ)-PET revealed findings consistent with cerebral damage to the affected temporal region. The memory deficit of the patient gradually improved in parallel with the relief of the sleep-related symptoms. FDG-PET showed considerable improvement in glucose metabolism when he had recovered, however, evidence of neural loss remained in the FMZ-PET findings.

Central μ-Opioidergic System Activation Evoked by Heavy and Severe-Intensity Cycling Exercise in Humans: a Pilot Study Using Positron Emission Tomography with 11C-Carfentanil

The central opioid receptor system likely contributes to the mechanism underlying the changes in affect elicited by exercise. Our aim was to use positron emission tomography (PET) to test whether exercise intensity influences activation of the μ-opioid receptor system in the brain, and whether changes in opioid receptor activation correlate with exercise-induced changes in affect. 7 healthy young male subjects (23±2 years) performed 20-min constant-load cycling exercises at heavy (ExH) and severe-intensity (ExS), and PET was performed using [11C]carfentanil as a tracer before and after each exercise. Exercise elicited the μ-opioidergic system activation in the large areas of the limbic system, particularly in the insular cortex, and cerebellum. Of note, deactivation of the μ-opioidergic system in the pituitary gland was identified as a specific finding in ExS, which evoked a distinctive sensation of fatigue. Within these brain areas, μ-opioid receptor activation correlated positively with increased positive affect (R2=0.67-0.95) in ExH and negative affect (R2=0.63-0.77) in ExS. These findings suggest that central μ-opioidergic neurotransmission evoked by continuous exercise is discriminated by work intensity. Notably, we also observed a possible contribution of the central μ-opioidergic system to the development of the sensation of fatigue during exhaustive exercise.