Association between health risks and frailty in relation to the degree of housing damage among elderly survivors of the great East Japan earthquake.

BACKGROUND: Many survivors of the Great East Japan Earthquake that occurred in 2011 were at risk of deteriorating health, especially elderly people living in disaster-stricken areas. The objectives of this prospective study were: a) to clarify the different lifestyle and psychosocial factors associated with frailty by sex among the non-disabled elderly survivors, and b) to describe the differences in characteristics stratified by the degree of disaster-related housing damage. METHODS: We followed 2261 Japanese survivors aged ≥65 years (45.3% male; mean age, 71.7 years) without disability or frailty who completed a self-administered questionnaire at baseline. All participants completed a baseline questionnaire in 2011 and at least one identical follow-up questionnaire between 2012 and 2015 regarding lifestyle (smoking status, alcohol intake, physical activity, sedentary lifestyle, and dietary intake) and psychosocial factors (self-rated health, standard of living, psychological distress, and social networks). Frailty was defined as a score of ≥5 on the Kihon Checklist, which is used by the Japanese government to certify the need for long-term care insurance. Adjusted odds ratios and 95% confidence intervals with frailty as the dichotomous dependent variable and health factors as the independent variables were calculated using a multilevel model for repeated measures by sex, followed by stratification analyses by the degree of housing damage. RESULTS: Over the 4-year study period, 510 participants (22.6%) developed frailty. In the post-disaster setting, many of the psychosocial factors remained more prevalent 4 years later among survivors with extensive housing damage. The presence of risk factors regarding the development of frailty differed by the degree of housing damage. Among men, psychological distress, in parallel with a poor social network, was related to frailty among only the participants with extensive housing damage and those living in temporary housing, whereas among women, worsening psychological distress was associated only with no damage and no displaced survivors. Among women with extensive damage and displacement, health outcomes such as overweight and diabetes and poor social networks were strongly related to frailty. CONCLUSIONS: Lifestyle and psychosocial factors associated with the risk of frailty differ by sex and the degree of housing damage.

Regional myocardial substrate uptake in hypertensive rats: a quantitative autoradiographic measurement.

Severe hypertension causes global and regional changes in myocardial perfusion and substrate utilization. Regional perfusion and fatty acid utilization were evaluated by dual-tracer autoradiography in normotensive and hypertensive rats of the Dahl strain. The regional distributions of perfusion and fatty acid utilization were homogeneous in normotensive rats. Severe hypertension was associated with a homogeneous pattern of regional perfusion, but fatty acid utilization was focally decreased in the free wall of the left ventricle. The decrease in fatty acid uptake was associated with a concomitant increase in glucose utilization. These findings suggest that severe hypertension is associated with uniform myocardial perfusion and focal alterations in the substrates used for the performance of myocardial work.

ICRP Publication 140: Radiological Protection in Therapy with Radiopharmaceuticals.

Radiopharmaceuticals are increasingly used for the treatment of various cancers with novel radionuclides, compounds, tracer molecules, and administration techniques. The goal of radiation therapy, including therapy with radiopharmaceuticals, is to optimise the relationship between tumour control probability and potential complications in normal organs and tissues. Essential to this optimisation is the ability to quantify the radiation doses delivered to both tumours and normal tissues. This publication provides an overview of therapeutic procedures and a framework for calculating radiation doses for various treatment approaches. In radiopharmaceutical therapy, the absorbed dose to an organ or tissue is governed by radiopharmaceutical uptake, retention in and clearance from the various organs and tissues of the body, together with radionuclide physical half-life. Biokinetic parameters are determined by direct measurements made using techniques that vary in complexity. For treatment planning, absorbed dose calculations are usually performed prior to therapy using a trace-labelled diagnostic administration, or retrospective dosimetry may be performed on the basis of the activity already administered following each therapeutic administration. Uncertainty analyses provide additional information about sources of bias and random variation and their magnitudes; these analyses show the reliability and quality of absorbed dose calculations. Effective dose can provide an approximate measure of lifetime risk of detriment attributable to the stochastic effects of radiation exposure, principally cancer, but effective dose does not predict future cancer incidence for an individual and does not apply to short-term deterministic effects associated with radiopharmaceutical therapy. Accident prevention in radiation therapy should be an integral part of the design of facilities, equipment, and administration procedures. Minimisation of staff exposures includes consideration of equipment design, proper shielding and handling of sources, and personal protective equipment and tools, as well as education and training to promote awareness and engagement in radiological protection. The decision to hold or release a patient after radiopharmaceutical therapy should account for potential radiation dose to members of the public and carers that may result from residual radioactivity in the patient. In these situations, specific radiological protection guidance should be provided to patients and carers.

Neuroprotective effect of chronic lithium treatment against hypoxia in specific brain regions with upregulation of cAMP response element binding protein and brain-derived neurotrophic factor but not nerve growth factor: comparison with acute lithium treatment.

OBJECTIVES: We evaluated the neuroprotective effect of chronically or acutely administered lithium against hypoxia in several brain regions. Furthermore, we investigated the contribution of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and cAMP response element binding protein (CREB) to the neuroprotective effect of lithium. METHODS: Brain slices were prepared from rats that had been treated chronically or acutely with lithium. The cerebral glucose metabolic rate (CMRglc) before and after hypoxia loading to brain slices was measured using the dynamic positron autoradiography technique with [(18)F]2-fluoro-2-deoxy-D-glucose. The changes of expression of proteins were investigated using Western blot analysis. RESULTS: Before hypoxia loading, the CMRglc did not differ between the lithium-treated and untreated groups. After hypoxia loading, the CMRglc of the untreated group was significantly lower than that before hypoxia loading. However, the CMRglc of the chronic lithium treatment group recovered in the frontal cortex, caudate putamen, hippocampus and cerebellum, but not in the thalamus. In contrast, the CMRglc of the acute lithium treatment group did not recover in any analyzed brain regions. After chronic lithium treatment, the levels of expression of BDNF and phospho-CREB were higher than those of untreated rats in the frontal cortex, but not in the thalamus. However, the expression of NGF did not change in the frontal cortex and thalamus. CONCLUSIONS: These results demonstrated that lithium was neuroprotective against hypoxia only after chronic treatment and only in specific brain regions, and that CREB and BDNF might contribute to this effect.

Abnormal pontine activation in pathological laughing as shown by functional magnetic resonance imaging.

To explore the aetiology of pathological laughing, a 65-year-old woman with pathological laughing was examined by 3-T functional magnetic resonance imaging (fMRI) before and after treatment with drugs. Here, we report that the patient consistently showed exaggerated pontine activation during the performance of three tasks before treatment, whereas abnormal pontine activation was no longer found after successful treatment with the selective serotonin reuptake inhibitor, paroxetine. Our findings in this first fMRI study of pathological laughing suggest that serotonergic replacement decreases the aberrant activity in a circuit that involves the pons.

Radiological protection in ion beam radiotherapy: practical guidance for clinical use of new technology.

Recently introduced technologies in radiotherapy have significantly improved the clinical outcome for patients. Ion beam radiotherapy, involving proton and carbon ion beams, provides excellent dose distributions in targeted tumours, with reduced doses to the surrounding normal tissues. However, careful treatment planning is required in order to maximise the treatment efficiency and minimise the dose to normal tissues. Radiation exposure from secondary neutrons and photons, particle fragments, and photons from activated materials should also be considered for radiological protection of the patient and medical staff. Appropriate maintenance is needed for the equipment and air in the treatment room, which may be activated by the particle beam and its secondary radiation. This new treatment requires complex procedures and careful adjustment of parameters for each patient. Therefore, education and training for the personnel involved in the procedure are essential for both effective treatment and patient protection. The International Commission on Radiological Protection (ICRP) has provided recommendations for radiological protection in ion beam radiotherapy in Publication 127 Medical staff should be aware of the possible risks resulting from inappropriate use and control of the equipment. They should also consider the necessary procedures for patient protection when new technologies are introduced into clinical practice.

Reciprocal ST-segment depression associated with exercise-induced ST-segment elevation indicates residual viability after myocardial infarction.

OBJECTIVES: We evaluated the clinical significance of reciprocal ST-segment depression associated with exercise-induced ST-segment elevation for detecting residual viability within the infarcted area. BACKGROUND: Although the relation between residual viability and exercise-induced ST-segment elevation has been described, there are no reports focusing on the relation between myocardial viability and reciprocal ST-segment depression associated with exercise-induced ST-segment elevation. METHODS: We evaluated regional blood flow and glucose utilization using N-13 ammonia (NH3) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in 30 patients with a previous Q-wave myocardial infarction (anterior in 15, inferior in 15). All subjects had single-vessel disease and had exercise-induced ST-segment elevations (> or =1 mm) in electrocardiographic leads. RESULTS: Reciprocal ST-segment depression (> or =1 mm) was present in 16 patients (Group A; anterior in 6, inferior in 10) but not in the remaining 14 patients (Group B). The degree of exercise-induced ST-segment elevation (1.8+/-0.2 vs. 2.0+/-0.2 mm) and the time from the onset of infarction to the study (75+/-49 vs. 74+/-52 days) did not differ between groups. There were no significant differences between groups in the severity of left ventricular dysfunction and the residual luminal narrowing in the infarct-related artery (45+/-21 vs. 48+/-25%). The presence and site of infarction were confirmed by NH3-PET in all patients. FDG-PET demonstrated residual tissue viability within infarct-related area in all patients in Group A and in 3 (21%) of 14 patients in Group B (p < 0.01). The sensitivity, specificity and accuracy of reciprocal ST-segment depression associated with exercise-induced ST-segment elevation for detecting residual viability were 84%, 100% and 90%, respectively. CONCLUSIONS: The occurrence of reciprocal ST-segment depression associated with exercise-induced ST segment elevation in patients with a previous Q-wave infarction who had single-vessel disease indicates residual tissue viability within the infarct-related area.

Pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody in murine experimental viral myocarditis.

The pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody Fab were investigated with use of murine experimental viral myocarditis as a model. The biodistribution of indium-111-labeled antimyosin antibody Fab on days 3, 5, 7, 14, 21 and 28 after encephalomyocarditis virus inoculation demonstrated that myocardial uptake increased significantly on days 5, 7 and 14 (maximum on day 7) in infected versus uninfected mice (p less than 0.001). In vivo kinetics in infected mice on day 7 demonstrated that the heart to blood ratio reached a maximum 48 h after the intravenous administration of indium-111-labeled antimyosin Fab, which was considered to be the optimal time for scintigraphy. The scintigraphic images obtained with indium-111-labeled antimyosin Fab demonstrated positive uptake in the cardiac lesion in infected mice. The pathologic study demonstrated that myocardial uptake correlated well with pathologic grades of myocardial necrosis. High performance liquid chromatography revealed the presence of an antigen-antibody complex in the circulation of infected mice after the injection of indium-111-labeled antimyosin Fab. This antigen bound to indium-111-labeled antimyosin Fab in the circulation might be whole myosin and this complex may decrease myocardial uptake and increase liver uptake. It is concluded that indium-111-labeled antimyosin monoclonal antibody Fab accumulates selectively in damaged heart tissue in mice with acute myocarditis and that indium-111-labeled antimyosin Fab scintigraphy may be a useful method for the visualization of acute myocarditis.

Stress thallium-201 transaxial emission computed tomography: quantitative versus qualitative analysis for evaluation of coronary artery disease.

Stress thallium-201 myocardial distribution was quantitatively evaluated by emission transaxial tomography in 104 patients who underwent coronary arteriography. The initial uptake and percent washout of thallium were assessed by the circumferential profile curves of the three short-axis sections and one middle right anterior oblique long-axis section. This quantitative tomographic analysis showed abnormal distribution in all but two patients (98%) with coronary artery disease, whereas qualitative analysis showed abnormality in 76 of the patients (93%). Quantitative analysis showed better sensitivity (91%) for detecting involved coronary vessels than qualitative analysis (80%, p less than 0.01), especially in three vessel disease (82 versus 67%, p less than 0.05). For localization of individual vessel involvement, quantitative analysis showed high sensitivity (right coronary artery: 96%, left anterior descending artery: 90% and left circumflex artery: 88%) as compared with qualitative analysis (88, 83 and 63%, respectively, p less than 0.05), while similar specificity was observed (92% for quantitative and 93% for qualitative analyses). Furthermore, in the study of patients without infarction, myocardial segments supplied by coronary vessels with moderate stenosis (51 to 75%) revealed abnormality more often with quantitative (81%) than with qualitative (56%) analysis. Thus, quantitative analysis of stress thallium emission tomography provides improved sensitivity for the detection of diseased coronary vessels in patients with three vessel disease and those with moderate stenosis. It is a valuable technique for the evaluation of coronary artery disease.

Prognostic value of an increase in fluorine-18 deoxyglucose uptake in patients with myocardial infarction: comparison with stress thallium imaging.

OBJECTIVES: This study was undertaken to evaluate the prognostic value of an increase in fluorine (F)-18 deoxyglucose uptake compared with clinical, angiographic and stress thallium findings in patients with myocardial infarction. BACKGROUND: Positron emission tomography (PET) imaging using F-18 deoxyglucose has been applied to assess tissue viability in patients with coronary artery disease. We hypothesized that patients with a myocardial segment with augmented F-18 deoxyglucose uptake are at high risk for a future cardiac event. METHODS: One hundred fifty-eight consecutive patients with myocardial infarction referred for F-18 deoxyglucose PET and stress thallium scans were studied. Follow-up was obtained in 84 patients at a mean interval of 23 months to investigate prognostic implications of radionuclide studies. RESULTS: Seventeen patients had a cardiac event during the follow-up interval. Univariate analysis showed that an increase in F-18 deoxyglucose uptake was the best predictor of a future cardiac event (p = 0.0006), followed by the number of stenosed vessels (p = 0.008). In the multivariate analysis, when an increase in F-18 deoxyglucose uptake was entered into the model, only angiographic variables had an independent prognostic value, whereas no other radionuclide variables showed significant prognostic value. Among patients who did not show redistribution, a future cardiac event was observed more often in patients with than in those without an increase in F-18 deoxyglucose uptake (p < 0.05). CONCLUSIONS: Thus, an increase in F-18 deoxyglucose uptake seemed to be the best predictor of a future cardiac event among all clinical, angiographic and radionuclide variables in this study of stable patients with myocardial infarction. Even when a stress thallium-201 scan does not show redistribution, those patients who have an increase in F-18 deoxyglucose uptake in a PET study may be at risk for a future cardiac event, and these patients may need aggressive treatment to prevent a future cardiac event.

Non-Q wave versus Q wave myocardial infarction: regional myocardial metabolism and blood flow assessed by positron emission tomography.

This study compared regional myocardial blood flow at rest and during supine exercise as well as regional myocardial glucose utilization in the fasting condition in 22 patients, 11 with antecedent non-Q wave and 11 with antecedent Q wave infarction. With use of N-13 (nitrogen-13) ammonia and F-18 (fluorine-18) deoxyglucose as tracers of blood flow and exogenous glucose utilization and positron emission tomography, hypoperfused areas were noted at rest and during exercise in all 11 patients (100%) with Q wave infarction. Among the 11 patients with non-Q wave infarction such areas were noted in only 5 (45%) at rest and in 8 (73%) during exercise. Furthermore, segmentally enhanced F-18 deoxyglucose uptake corresponding to the infarcted areas (identified electrocardiographically) was seen in 10 (91%) of the 11 patients with non-Q wave infarction but in only 4 (36%) of the 11 patients with Q wave infarction (p less than 0.01). In conclusion, segmental F-18 deoxyglucose uptake as a possible sign of myocardial viability was seen more frequently in non-Q wave than in Q wave infarction and, importantly, regionally enhanced F-18 deoxyglucose uptake occurred even in the absence of segmental rest or exercise blood flow abnormalities, or both, in 5 (45%) of 11 patients with non-Q wave infarction.

Noninvasive quantitative measurements of regional cerebral blood flow using technetium-99m-L,L-ECD SPECT activated with acetazolamide: quantification analysis by equal-volume-split 99mTc-ECD consecutive SPECT method.

Resting- and acetazolamide (Acz)-activated-regional cerebral blood flow (rCBF) measurements were performed by consecutive single-photon emission computed tomography (SPECT) studies before and after Acz administration using equal-volume-split technetium-99m-L,L-ethyl cysteinate dimer. Quantitative rCBF images were converted from qualitative axial SPECT images by the application of Patlak plot graphical analysis with radionuclide angiography and Lassen's linearization correction. Total time span required for this study was 53 minutes. The unaffected side of 37 studies with unilateral vascular lesions and 45 studies without apparent vascular lesions showed 132 +/- 17% and 140 +/- 15% increase of mean CBF (mCBF), respectively, under Acz administration. Comparing these values, the Acz-activated rCBF increases of less-affected and affected hemispheres of 23 studies with bilateral vascular lesions (116 +/- 13% and 113 +/- 12%, respectively) was lower with high statistical significance (P < 0.001). For the other 20 cases, physiologic saline was administered instead of Acz. This group showed no changes in mCBF under placebo administration (after placebo/baseline; 100 +/- 6%). Acetazolamide-activated rCBF increase was recognized clearly and easily using quantitative images. This noninvasive method is easy to perform and may be helpful to detect regional abnormalities of hemodynamic reserve in cerebrovascular diseases.

Cholinergic projection from the basal forebrain and cerebral glucose metabolism in rats: a dynamic PET study.

To investigate the influence of cholinergic projections from the basal forebrain on cerebral cortex metabolism, we evaluated the cerebral metabolic rate of glucose (CMRGlu) after selective inhibition of cholinergic neurons in the rat basal forebrain using the pyruvate dehydrogenase complex inhibitor 3-bromopyruvic acid (BPA), and compared the results with those obtained after lesioning the basal forebrain with ibotenic acid, as well as with those from a sham-operated control group. CMRGlu was measured using positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG). Three days after surgery, CMRGlu and k3 (phosphorylation of FDG) were reduced similarly in the frontal cortex on the BPA-injected side and in the ibotenic acid-treated group, whereas K1 (transport rate of FDG from the plasma to brain) showed no marked changes. At 3 weeks postoperatively, the CMRGlu and k3 of the frontal cortex in both groups recovered to levels similar to those of the sham-operated group. The main difference between the BPA and ibotenic acid groups was that CMRGlu showed mild reduction on the side contralateral to the operation in the former, while such reduction was confined to the ipsilateral hemisphere in the latter. The present results indicate that the cholinergic system in the basal forebrain regulates cerebral cortex glucose metabolism through direct excitation of cortical neurons.

Brain perfusion SPECT with 99mTc-bicisate: comparison with PET measurement and linearization based on permeability-surface area product model.

To characterize a recently introduced cerebral perfusion tracer, 99mTc-bicisate, single photon emission computed tomography (SPECT) images of 99mTc-bicisate were compared with CBF images obtained by positron emission tomography (PET) using the 15O steady-state method in 10 cases of cerebrovascular disease and dementia. 99mTc-Bicisate SPECT and PET CBF images showed a similar distribution pattern except for two cases with subacute stroke, in which 99mTc-bicisate showed less uptake than CBF in the infarcted area where oxygen metabolism was severely diminished. Comparison of 99mTc-bicisate uptake and CBF in the other eight cases showed less contrast between high- and low-flow regions in 99mTc-bicisate SPECT. Although the SPECT count ratio of cerebral structures to cerebellum showed a good correlation with CBF ratio, it gradually deviated from the linear relationship in the high-flow range. Assuming this nonlinear relationship is due to the limited extraction of the tracer, we estimated the permeability-surface area product (PS) value by a nonlinear least-squares curve-fitting procedure. The correction of the nonlinear relationship using the estimated PS value and a table lookup method resulted in an excellent linear relationship between corrected SPECT counts and CBF.

Selective cerebral hematocrit decrease in the centrum semiovale after carotid artery occlusion: a PET study.

The centrum semiovale may be susceptible to hypoperfusion as a result of carotid artery occlusion. Recent studies suggest that the cerebral hematocrit decreases with diminished cerebral perfusion pressure. To investigate whether the effect of carotid artery occlusion on the hematocrit in the centrum semiovale is different from that in the cerebral cortex, seven patients with unilateral carotid artery occlusion were studied with positron emission tomography. The distributions of the red blood cell and plasma volumes were assessed using carbon monoxide labeled with oxygen 15 and human serum albumin-dithiosemicarbazone tracers labeled with copper 62, respectively. The CBF and CMRO2 were also measured with the (15)O steady-state technique. The calculated values for the hematocrit in the centrum semiovale ipsilateral to the arterial occlusion were significantly decreased compared with those in any of the other regions examined (the overlying cortical region and the contralateral cortex and centrum semiovale). This decrease in hematocrit, which resulted from a more pronounced increase in plasma volume than in red blood cell volume, was associated with a decrease in CBF and an increase in the oxygen extraction fraction. Hemodynamic disturbance caused by carotid artery occlusion may induce selective decrease of hematocrit limited to the centrum semiovale.

Hypoxic but not ischemic neurotoxicity of free radicals revealed by dynamic changes in glucose metabolism of fresh rat brain slices on positron autoradiography.

Dynamic changes in the regional cerebral glucose metabolic rate induced by hypoxia/reoxygenation or ischemia/reperfusion were investigated with a positron autoradiography technique. Fresh rat brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [18F]FDG uptake in the slices were obtained. In the case of loading hypoxia (oxygen deprivation)/pseudoischemia (oxygen and glucose deprivation) for various periods of time, the net influx constant (K) of [18F]FDG at preloading and after reoxygenation/pseudoreperfusion (post-loading) was quantitatively evaluated by applying the Patlak graphical method to the image data. Regardless of the brain region, with hypoxia lasting > or =20 minutes, the postloading K value was decreased compared with the unloaded control, whereas with pseudoischemia of < or =40 minutes, approximately the same level as the unloaded control was maintained. Next, the neuroprotective effect against hypoxia/pseudoischemia loading induced by the addition of a free radical scavenger or an N-methyl-D-aspartate (NMDA) antagonist was assessed by determining whether a decrease in the postloading K value was prevented. Whereas with 20-minute hypoxia, both agents exhibited a neuroprotective effect, in the case of 50-minute pseudoischemia, only the NMDA antagonist did so, with the free radical scavenger being ineffective. These results demonstrate that hypoxia causes irreversible neuronal damage within a shorter period than ischemia, with both free radicals and glutamate suggested to be involved in tandem in the neurotoxicity induced by hypoxia, whereas glutamate alone is involved in ischemic neurotoxicity.

Use of 2-deoxy-D[1-11C]glucose for the determination of local cerebral glucose metabolism in humans: variation within and between subjects.

The deoxyglucose technique for the measurement of local cerebral glucose metabolism (LCMRgl) has been widely applied in animals utilizing 14C-deoxyglucose and in humans employing 18F-fluorodeoxyglucose. Repeat studies in humans over a relatively brief period of time have not been possible because of the 110-min half-life of fluorine-18. With the synthesis of 11C-deoxyglucose it has now become possible to utilize this short-lived (20 min) tracer for the measurement of LCMRgl and to determine its variability within subjects over a 2-h period. The kinetic rate constants for 11C-deoxyglucose were determined for gray and white matter and found to be very similar to those for 18F-fluorodeoxyglucose, suggesting that these two analogues of glucose have similar affinities for the facilitated transport system and are similar substrates for hexokinase in the brain. The coefficient of variation of repeated measurements of LCMRgl in a series of six normal subjects was 5.5% to 8.7% for various gray matter structures and 9.7% and 14.0% for white matter structures. The pattern of cerebral metabolic rates is relatively constant in a given individual when the conditions of the study are unchanged. The ability to make repeat measurements in the same subject reduces the variance due to between-subject differences, allowing smaller changes in LCMRgl to be detected with confidence.

SPECT with [99mTc]-d,l-hexamethyl-propylene amine oxime (HM-PAO) compared with regional cerebral blood flow measured by PET: effects of linearization.

In order to validate the use of technetium-99m-d,l-hexamethylpropyleneamine oxime (HM-PAO) as a flow tracer, a total of 21 cases were studied with single photon emission computerized tomography (SPECT), and compared to regional cerebral blood flow (rCBF) measured by position emission tomography (PET) using the oxygen-15 CO2 inhalation technique. Although HM-PAO SPECT and rCBF PET images showed a similar distribution pattern the HM-PAO SPECT image showed less contrast between high and low activity flow regions than the rCBF image and a nonlinear relationship between HM-PAO activity and rCBF was shown. Based on the assumption of flow-dependent backdiffusion of HM-PAO from the brain, we applied a "linearization algorithm" to correct the HM-PAO SPECT images. The corrected HM-PAO SPECT images revealed a good linear correlation with rCBF (r = 0.901, p less than 0.001). The results indicated HM-PAO can be used as a flow tracer with SPECT after proper correction.

A multicenter validation of regional cerebral blood flow quantitation using [123I]iodoamphetamine and single photon emission computed tomography.

Recently, two methods have been proposed for regional cerebral blood flow (rCBF) quantitation using [123I]iodoamphetamine (IMP) and single-photon emission computed tomography (SPECT). The table look-up (TLU) method has been shown to provide both rCBF and volume of distribution, Vd, images from two SPECT scans, while a single-scan autoradiographic (ARG) technique provided rCBF using a fixed and assumed Vd. In both methods, a single blood sample was referred to calibrate the previously determined standard input function. The present multicenter project was designed to evaluate the accuracy of both methods for use as clinical investigative tools. Ten independent institutions performed [123I]IMP-SPECT studies according to both methods in 76 subjects (10 normal volunteers, 32 patients with cerebrovascular disease, and 34 patients with other diseases). Calculated rCBF values were compared with those obtained by the following reference methods available in the participating institutions; [15O] H2O positron emission tomography (PET) (five institutions), [133Xe]SPECT (four institutions), and the [123I]IMP microsphere method (three institutions). Both ARG and TLU methods provided rCBF values that were significantly correlated with those measured by the [15O] H2O PET technique (p < 0.001 for all subjects; overall regression equation, y = 15.14 + 0.54x) and those measured by the [123I]IMP-microsphere method (p < 0.001 for all subjects: y = 2.0 + 0.80x). Significant correlation (p < 0.05) was observed in 18 of 24 subjects studied with the [133Xe] SPECT reference technique (overall regression equation, y = 15.0 + 0.55x). Mean cortical gray matter rCBF in a group of normal subject was 43.9 +/- 3.3 and 43.4 +/- 2.0 ml/min/100 g for the ARG and TLU methods, respectively. Regional Vd of [123I]IMP estimated by the TLU method was 45 ml/ml +/- 20% in the normal cortical region. Close agreement between ARG and TLU rCBF values was observed (y = -3.21 + 1.07x, r = 0.97), confirming the validity of assuming a fixed Vd in the ARG method. Results of this study demonstrate that both the ARG and TLU methods accurately and reliably estimate rCBF in a variety of clinical settings.

A milestone for normal development of the infantile brain detected by functional MRI.

OBJECTIVE: To investigate the relationship between cerebral cortical function and white matter myelination in the visual pathway in the evaluation of normal brain development. METHODS: The authors performed quantitative analysis of white matter myelination detected with conventional T1-weighted spin echo (SE) MRI and brain functional MRI (fMRI) using echoplanar imaging with photic stimulation in 27 neurologically normal infants (age range, 0 to 22 weeks). RESULTS: An age-dependent gradual increase in signal intensity was observed in optic radiation on the T1-weighted SE images, indicating progression of white matter myelination. A rapid age-dependent reverse in signal response was observed on fMRI. Infants older than 8 weeks showed a stimulus-induced signal decrease in the visual cortex, whereas infants younger than 7 weeks showed a signal increase. CONCLUSIONS: A rapid inversion of response revealed by fMRI with photic stimulation in infants suggests a change in oxygen consumption during neuronal activation, which is related to rapid synapse formation and accompanying increased metabolism. fMRI can detect dynamic metabolic changes during brain maturation, which is a different developmental process from white matter myelination. The metabolic changes detected by fMRI provide a milestone for the evaluation of normal brain development.