Relationship between the housing coldness/warmth evaluation by CASBEE Housing Health Checklist and psychological distress based on TMM Community-Based Cohort Study: a cross-sectional analysis.

OBJECTIVES: Previous studies have reported the relationship between housing environment and health, although due to cost and effort, it was difficult to conduct housing condition surveys on a large scale. The CASBEE Housing Health Checklist (the Checklist) made it possible to easily evaluate the housing condition from the resident's perspective. This study examined the relationship between housing coldness/warmth evaluation using the Checklist and psychological distress in a large-scale general Japanese population. STUDY DESIGN: A cross-sectional study. METHODS: We analysed data from 29,380 people aged ≥20 years who lived in Miyagi Prefecture, Japan. As an assessment of housing coldness/warmth, we used the Checklist. We classified participants' total scores on the Checklist related to coldness/warmth into quartiles. The Kessler 6 scale was used as an indicator of psychological distress. Multivariable logistic regression models were used to estimate the adjusted odds ratio (OR) and 95% confidence intervals (CIs). Adjusted OR and P-values for linear trends were calculated using the quartiles of the Checklists' score. RESULTS: Among participants in Q1 (i.e., poorer subjective house condition), the percentage of people with psychological distress was high. Compared to the highest quartile, Q1 showed poorer evaluation of housing coldness/warmth, and higher OR for psychological distress. The OR (95% CI) of psychological distress for Q3, Q2, and Q1 compared with Q4 were 1.93 (1.74-2.14), 2.82 (2.55-3.12), and 5.78 (5.25-6.35), respectively. CONCLUSIONS: Housing coldness/warmth evaluation was significantly related to psychological distress. This finding suggests that maintaining a comfortable thermal environment at home could be important for residents' mental health.

Bridging macroscopic and microscopic methods for the measurements of cerebral blood flow: Toward finding the determinants in maintaining the CBF homeostasis.

Methods exist to evaluate the cerebral blood flow (CBF) at both the macroscopic and microscopic spatial scales. These methods provide complementary information for understanding the mechanism in maintaining an adequate blood supply in response to neural demand. The macroscopic CBF assesses perfusion flow, which is usually measured using radioactive tracers, such as diffusible, nondiffusible, or microsphere. Each of them determines CBF based on indicator dilution principle or particle fraction principle under the assumption that CBF is steady state during the measurement. Macroscopic CBF therefore represents averaged CBF over a certain space and time domains. On the other hand, the microscopic CBF assesses bulk flow, usually measures using real-time microscopy. The method assesses hemodynamics of microvessels, ie, vascular dimensions and flow velocities of fluorescently labeled or nonlabeled RBC and plasma markers. The microscopic CBF continuously fluctuates in time and space. Smoothing out this heterogeneity may lead to underestimation in the macroscopic CBF. To link the two measurements, it is needed to introduce a common parameter which is measurable for the both methods, such as mean transit time. Additionally, applying the defined physiological and/or pharmacological perturbation may provide a good exercise to determine how the specific perturbations interfere the quantitative relationships between the macroscopic and microscopic CBF. Finally, bridging these two-scale methods potentially gives a further indication how the absolute CBF is regulated with respect to a specific type of the cerebrovascular tones or capillary flow velocities in the brain.

Commentary and opinion: I. Principal component analysis, variance partitioning, and "functional connectivity".

We briefly review the need for careful study of "variance partitioning" and "optimal model selection" in functional positron emission tomography (PET) data analysis, emphasizing the use of principal component analysis (PCA) and the importance of data analytic techniques that allow for heterogeneous spatial covariance structures. Using an [15O]water dataset, we demonstrate that--even after data processing--the intrasubject signal component of primary interest in baseline activation studies constitutes a very small fraction of the intersubject variance. This small intrasubject variance component is subtly but significantly changed by using analysis of covariance instead of scaled subprofile model processing before applying PCA. Finally, we argue that the concept of "functional connectivity" should be interpreted very generally until the relative roles of inter- and intrasubject variability in both disease and normal PET datasets are better understood.

Tomographic mapping of kinetic rate constants in the fluorodeoxyglucose model using dynamic positron emission tomography.

A quick computing algorithm to calculate the rate constants (k*1, k*2, k*3) in the [18F]2-fluoro-2-deoxy-D-glucose (FDG) model was developed. The algorithm solved for the rate constants pixel by pixel using a conventional least-squares method and two tables consisting of a set of various rate constants, to shorten the computing time. Five planes of rate constant images were obtained. A combined study using the dynamic FDG method and the 15O-labeled gas continuous inhalation method was performed on seven healthy male volunteers aged 26-35 years. Results indicated an apparent discrepancy between CMRglu and CMRO2 in the cerebellum, where the low glucose utilization was correlated with a low FDG phosphorylation rate (k*3) despite a sufficient FDG transportation rate (k*1) from plasma to tissue.

A new approach of weighted integration technique based on accumulated images using dynamic PET and H2(15)O.

We developed a new technique of weighted integration for the measurement of local cerebral blood flow (LCBF) and the blood-tissue partition coefficient (p) using dynamic positron emission tomography (PET) and H2(15)O. The weighted integration in the new technique is carried out on the equation of the first time integration of the Kety-Schmidt differential equation. Practically, serially accumulated images with sequentially prolonged accumulation times are weighted by two arbitrary functions. The weighting functions do not have to be differentiated because of the exclusion of the differential term in the starting equation. Consequently, the method does not require data at the end of the scan. The technique was applied to H2(15)O dynamic PET performed on four normal subjects, and was verified to provide a better signal-to-noise ratio than the previously developed integrated projection (IP) technique. Computer simulations were carried out to investigate the effects of statistical noise, tissue heterogeneity, and time delay and dispersion in arterial input function. The simulation showed that the new technique provided about a 1.4 times lower statistical error in both LCBF and p at 50 ml 100 g-1 min-1 compared to the IP technique, and it should be noted that the new technique was less sensitive to the shape of the weighting functions. The new technique provides a new strategy with respect to the statistical error for estimation of LCBF and p.

Changes in human regional cerebral blood flow and cerebral blood volume during visual stimulation measured by positron emission tomography.

The hemodynamic mechanism of increase in cerebral blood flow (CBF) during neural activation has not been elucidated in humans. In the current study, changes in both regional CBF and cerebral blood volume (CBV) during visual stimulation in humans were investigated. Cerebral blood flow and CBV were measured by positron emission tomography using H(2)(15)O and (11)CO, respectively, at rest and during 2-Hz and 8-Hz photic flicker stimulation in each of 10 subjects. Changes in CBF in the primary visual cortex were 16% +/- 16% and 68% +/- 20% for the visual stimulation of 2 Hz and 8 Hz, respectively. The changes in CBV were 10% +/- 13% and 21% +/- 5% for 2-Hz and 8-Hz stimulation, respectively. Significant differences between changes in CBF and CBV were observed for visual stimulation of 8 Hz. The relation between CBF and CBV values during rest and visual stimulation was CBV = 0.88CBF(0.30). This indicates that when the increase in CBF during neural activation is great, that increase is caused primarily by the increase in vascular blood velocity rather than by the increase in CBV. This observation is consistent with reported findings obtained during hypercapnia.

Linearization correction of 99mTc-labeled hexamethyl-propylene amine oxime (HM-PAO) image in terms of regional CBF distribution: comparison to C15O2 inhalation steady-state method measured by positron emission tomography.

The radioisotope distribution following intravenous injection of 99mTc-labeled hexamethylpropyleneamine oxime (HM-PAO) in the brain was measured by single photon emission computed tomography (SPECT) and corrected for the nonlinearity caused by differences in net extraction. The "linearization" correction was based on a three compartment model, and it required a region of reference to normalize the SPECT image in terms of regional cerebral blood flow distribution. Two different regions of reference, the cerebellum and the whole brain, were tested. The uncorrected and corrected HM-PAO images were compared with cerebral blood flow (CBF) image measured by the C15O2 inhalation steady state method and positron emission tomography (PET). The relationship between uncorrected HM-PAO and PET-CBF showed a correlation coefficient of 0.85 but tended to saturate at high CBF values, whereas it was improved to 0.93 after the "linearization" correction. The whole-brain normalization worked just as well as normalization using the cerebellum. This study constitutes a validation of the "linearization" correction and it suggests that after linearization the HM-PAO image may be scaled to absolute CBF by employing a global hemispheric CBF value as measured by the nontomographic 133Xe clearance method.

Error analysis of a quantitative cerebral blood flow measurement using H2(15)O autoradiography and positron emission tomography, with respect to the dispersion of the input function.

The effect of the inaccuracy of the input function on CBF measured by the H2(15)O autoradiographic method was investigated. In H2(15)O autoradiography the measured input function usually includes a larger dispersion than the true input function, as well as the absolute time axis having been already lost. The time constant of the external dispersion that occurred in our continuous sampling system was evaluated as 10-12 s when the dispersion function was approximated by a monoexponential function. The internal dispersion occurring in arterial lines in a human body was evaluated as 4-6 s. Such dispersion, indispensable in a patient study, was found to produce large errors in calculating CBF, e.g., 5(10) s of the dispersion caused +15(33) and +10(20)% systematic overestimations for the 40- and 60-s accumulation time respectively. An analytical correction employing an inverse Laplace transform was applied to clinical CBF studies, and the results were compared with those from the C15O2 steady-state inhalation method. Correction by 10 s in time constant, corresponding to the external dispersion, reduced the overestimation significantly from 70-100% to approximately 20%. Further correction by 5 s, corresponding to the internal dispersion, resulted in a negligible difference (less than a few percent) from the steady-state method.

A determination of the regional brain/blood partition coefficient of water using dynamic positron emission tomography.

In order to investigate the validity of the single compartment model in measuring CBF with the use of 15O-labeled water (H2 15O), dynamic positron emission tomography (PET) was performed following bolus injection of H2 15O. Careful attention was paid to accuracy in the measurement system (especially for the input function). In the region of the putamen, which includes the smallest mixture of gray and white matters in addition to the smallest contamination of cerebrospinal fluid (CSF) spaces, the partition coefficient obtained was 0.88 +/- 0.06 (ml/g). The discrepancy from the prediction estimated from the brain/blood water content ratio was only 7%. This finding suggests that there is no more complicated model than the usual single compartment one to describe the physiological behaviour of 15O water. On the other hand, in the other cortical regions, the discrepancy was larger (e.g., about 12% for the insular cortex and 26% for the frontal cortex) than in the region of the putamen, and a significant fit-interval dependence was observed in the calculated parameters. These observations suggest a significant effect of tissue heterogeneity and/or contamination with nonperfusable spaces in actual clinical PET data.

Regional differences in cerebral vascular response to PaCO2 changes in humans measured by positron emission tomography.

Hypercapnia and hypocapnia produce cerebral vasodilation and vasoconstriction, respectively. However, regional differences in the vascular response to changes in Paco2 in the human brain are not pronounced. In the current study, these regional differences were evaluated. In each of the 11 healthy subjects, cerebral blood flow (CBF) was measured using 15O-water and positron emission tomography at rest and during hypercapnia and hypocapnia. All CBF images were globally normalized for CBF and transformed into the standard brain anatomy. t values between rest and hypercapnia or hypocapnia conditions were calculated on a pixel-by-pixel basis. In the pons, cerebellum, thalamus, and putamen, significant relative hyperperfusion during hypercapnia was observed, indicating a large capacity for vasodilatation. In the pons and putamen, a significant relative hypoperfusion during hypocapnia, that is, a large capacity for vasoconstriction, was also observed, indicating marked vascular responsiveness. In the temporal, temporo-occipital, and occipital cortices, significant relative hypoperfusion during hypercapnia and significant relative hypoperfusion during hypocapnia were observed, indicating that cerebral vascular tone at rest might incline toward vasodilatation. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve by hypercapnia and in the correction of CBF measurements for variations in subjects' resting Paco2.

Oxygen extraction fraction at maximally vasodilated tissue in the ischemic brain estimated from the regional CO2 responsiveness measured by positron emission tomography.

The oxygen extraction fraction (OEF) at maximally vasodilated tissue in patients with chronic cerebrovascular disease was evaluated using positron emission tomography. The vascular responsiveness to changes in PaCO2 was measured by the H2(15)O autoradiographic method. It was correlated with the resting-state OEF, as estimated using the 15O steady-state method. The subjects comprised 15 patients with unilateral or bilateral occlusion and stenosis of the internal carotid artery or middle cerebral artery or moyamoya disease. In hypercapnia, the scattergram between the OEF and the vascular/responsiveness to changes in PaCO2 revealed a significant negative correlation in 11 of 19 studies on these patients, and the OEF at the zero cross point of the regression line with a vascular responsiveness of 0 was 0.53 +/- 0.08 (n = 11). This OEF in the resting state corresponds to exhaustion of the capacity for vasodilation. The vasodilatory capacity is discussed in relation to the lower limit of autoregulation.

Evaluation of regional differences of tracer appearance time in cerebral tissues using [15O] water and dynamic positron emission tomography.

The tracer appearance time relative to the radial artery-sampling site has been evaluated in six brain locations in five human subjects using dynamic positron emission tomography (PET) following the bolus injection of H2(15)O. There was a maximum difference of +/- 2 s from the average in each location. To globally adjust the timing difference between the measured arterial curve and the PET scan, a correction method was developed based on a nonlinear least-squares fitting procedure. This new technique determined the global time delay with an accuracy of +/- 0.5 s. On the other hand, the linear backward extrapolation method resulted in a systematic error of 4 s.

Cerebral uptake of 99mTc-bicisate in patients with cerebrovascular disease in comparison with CBF and CMRO2 measured by positron emission tomography.

The regional brain uptake of 99mTc-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethyl ester (99mTc-bicisate) measured by single photon emission computed tomography (SPECT) was compared with the regional CBF and CMRO2 measured by positron emission tomography in patients with cerebrovascular disease. Nine patients with the diagnosis of cerebral ischemic disorders (n = 7) or cerebral hemorrhage (n = 2) were studied. 99mTc-Bicisate brain uptake correlated with CBF and CMRO2. However, 99mTc-bicisate uptake did not reflect CBF in the single lesion showing luxury perfusion, which seemed to resemble a CMRO2 image. Though quantitative analysis showed the nonlinear correspondence of 99mTc-bicisate brain uptake with CBF and CMRO2, this correspondence could be corrected into a more linear relationship using a correction factor. 99mTc-Bicisate washout from the brain had no correlation to CBF and CMRO2. This diffuse decreasing washout rate was approximately 15% during the first hour after injection. By using the lipophilic fraction of arterial blood and a linearized correction of 99mTc-bicisate SPECT images, the feasibility of obtaining a factor-related CBF and CMRO2 was suggested from our data. These results suggested that 99mTc-bicisate had good characteristics for routine clinical use with SPECT to display the brain function in patients with neurological disorders.

A system for cerebral blood flow measurement using an H215O autoradiographic method and positron emission tomography.

A system for CBF measurement using an H215O autoradiographic method and positron emission tomography (PET) has been designed and installed as a clinical tool. Following an intravenous injection of H215O, a radioactivity accumulation in the brain tissue for 60 s and a continuous record of radioactivity in arterial blood were measured by a high counting speed PET device and a beta-ray detector, respectively, and CBF was calculated by a table-lookup procedure. First, this method was compared with the C15O2 inhalation steady-state method on 17 cerebrovascular disease patients and four normal subjects. The two values for CBF agreed with each other when H215O autoradiographic method was applied by correction for the dispersion in the measured arterial radioactivity-time curve. However, without the correction, the CBF by the H215O autoradiographic method revealed substantial overestimation by 30.6 +/- 17.5%. A reduced gray/white ratio of CBF was also observed in the H215O autoradiographic method. Second, simulation was performed in order to determine optimal accumulation time by PET scan; the result was that errors due to dispersion and time mismatch became critical as the accumulation time was shortened to less than 60 s.

Photic stimulation study of changing the arterial partial pressure level of carbon dioxide.

To investigate the effect of the level of baseline cerebral blood flow (CBF) on local CBF augmentation by activation, we have used positron emission tomography to measure regional CBF (rCBF) in 12 normal volunteers with and without photic stimulation during hypocapnia, normocapnia, and hypercapnia. The increase in rCBF in the primary visual cortex by photic stimulation was 10.8 +/- 3.1, 18.6 +/- 9.3, and 19.5 +/- 6.1 ml 100 ml-1 min-1 in hypo-, normo-, and hypercapnia, respectively. The increase was significantly smaller in hypocapnia than in normocapnia (p < 0.005). The fractional CBF increase caused by the photic stimulation was the same in all breathing conditions. This result indicates that the magnitude of the CBF increase induced by neuronal activity correlates proportionally with the level of baseline CBF.

Measurement of cerebral blood flow using bolus inhalation of C15O2 and positron emission tomography: description of the method and its comparison with the C15O2 continuous inhalation method.

This article describes a rapid method for the regional measurement of cerebral blood flow using a single breath of C15O2 and positron emission tomography. The technique is based on the bolus distribution principle and utilises a reference table for the calculation of flow. Seven subjects were studied using both this method and the C15O2 continuous inhalation steady-state technique. The single-breath method gave flow values 20% higher than those obtained using the steady-state method. A simulation study was performed in an attempt to define the reasons for the difference between the two techniques. Estimations were made of identified sources of error in the measurement of regional cerebral blood flow using the single-breath technique and compared with results from a similar study previously described for the steady-state technique. However, further comparative studies will be necessary to satisfactorily explain the difference between both techniques.

Optimal scan time of oxygen-15-labeled water injection method for measurement of cerebral blood flow.

We investigated the optimal scan time for obtaining the maximal signal-to-noise (S/N) ratio in cerebral blood flow (CBF) measured by PET imaging following 15O-water bolus injection. We performed sequential measurements with dynamic scans of six subjects injected at rest while listening to white noise. Each dynamic data set was edited into images corresponding to different scan times and were calibrated to CBF images by the table look-up method. For each scan time, we evaluated a pixel-by-pixel standard deviation of the CBF for sequential measurements. The S/N-ratio of CBF in the gray matter was 10.2 +/- 1.7 and 13.6 +/- 2.9 at a 40 and 120 sec scan time, respectively. The gain of the 120-sec over 40-sec scan time corresponds to an 80% increase in the number of trials to reach the same S/N-ratio in a stimulation-activation study. The simulation study supported the results, in which the maximal S/N-ratio of the CBF was demonstrated to be 90 and 120 sec at a CBF of 80 and 60 ml/100 ml/min, respectively. It is concluded that the optimal scan time of the 15O-water bolus injection method is in the interval from 90 to 120 sec.

A new graphic plot analysis for cerebral blood flow and partition coefficient with iodine-123-iodoamphetamine and dynamic SPECT validation studies using oxygen-15-water and PET.

To estimate regional cerebral blood flow (rCBF) and brain-blood partition coefficient (lambda) using a dynamic measurement, a new graphic plot analysis is proposed. By assuming a two-compartment model for tracer kinetics, we derived the linear relationship as Y(t) = K1 - k2 X(t), where Y(t) is the ratio of brain tissue activity-to-time-integrated arterial blood activity and X(t) is the ratio of time-integrated brain tissue activity-to-time-integrated arterial blood activity. A plot of Y(t) against X(t) yields a straight line and the y- and x-intercept of the regression line represent rCBF (K1) and lambda, respectively. The slope is a washout constant (-k2). This method was applied to 14 subjects with N-isopropyl-p-iodine-123 iodoamphetamine ([123I]IMP). The mean values of K1 and lambda for normal subjects were 41.3 +/- 6.7 ml/100 g/min and 29.6 +/- 6.5 ml/g, respectively, in the gray matter. A comparative study with positron emission tomography (PET) using an H2(15)O autoradiographic method revealed good correlation between IMP K1 and PET rCBF [r = 0.822; K1 = 0.842 rCBF + 0.030 (ml/g/min)]. The values of K1 using the graphical method were in excellent agreement with those using a nonlinear least-squares fitting technique (r = 0.992 for K1; r = 0.941 for lambda). The estimated K1 values in the graphical method were not changed when scanning times were varied. We conclude that a two-compartment model is acceptable for IMP kinetics within a scan time of 60 min. The graphical method gives a reliable and rapid estimation of rCBF when applied to dynamic data.

Deadtime correction method using random coincidence for PET.

A deadtime correction method is proposed for quantitative measurements in positron emission tomography. The correction is based on the observation that a deadtime loss of the random coincidence events corresponds to that of the single events and of the total coincidence events. Using the proposed correction method, the deadtime loss was kept within 1% up to the true coincidence rate of 50 X 10(3) cps per plane for a cylindrical phantom of 20 cm in diameter. Accuracy of the method is confirmed to be independent of the size of the object.

Automated interstudy image registration technique for SPECT and PET.

UNLABELLED: We report the extended application of an automated computer technique for three-dimensional spatial registration of SPECT and PET studies. METHODS: The technique iteratively reslices a misaligned data set until the sum of the absolute differences (SAD) from a reference data set is minimized. The registration accuracy was assessed in Hoffman brain phantom studies collected with known misalignments and transmission studies of a thorax phantom with fiducial markers. The SAD was compared with three other cost functions: stochastic sign change criterion, sum of products and standard deviation (s.d.) of ratios. In clinical neurological and myocardial perfusion studies, registration accuracy was estimated from the relative locations of landmarks in the reference and registered data sets. RESULTS: Registration accuracy in the Hoffman brain phantom studies was -0.07 +/- 0.46 mm (mean +/- s.d.) for translations and -0.01 +/- 0.20 degrees for rotations, with maximum translation and rotation errors of 1.2 mm and 0.8 degree, respectively. The SAD was the most accurate and reliable cost function. Registration errors in the thorax phantom were 3.1 +/- 1.7 mm. Mean accuracy in the neurological studies, estimated from landmark pairs, was 2.0 +/- 1.1 mm for SPECT to SPECT and 1.8 +/- 1.1 mm for PET to SPECT registrations. Average registration accuracy in 201Tl myocardial perfusion studies was 2.1 +/- 1.2 mm. CONCLUSION: Our registration method (a) provided accurate registrations for phantom and clinical SPECT and PET studies, (b) is fully automated, (c) simplifies comparison of data sets obtained at different times and with different modalities, and (d) can be applied retrospectively.