Non-invasive methods for absolute cerebral blood flow measurement using 99mTc-ECD: a study in healthy volunteers

Radionuclide angiography with technetium-99m ethyl cysteinate dimer (ECD) allows non-invasive estimation of absolute cerebral blood flow (CBF), either by graphical Patlak-Gjedde analysis (PGA) or by spectral analysis (SA). Other methods estimate CBF by means of single-point arterial or venous sampling. The aim of this study was to evaluate radionuclide scanning and single-point venous sampling as potential clinical non- to minimally invasive methods for CBF determination in a large set of carefully screened healthy volunteers over the adult age range. Eighty-three carefully screened healthy volunteers (20-81 years, 43 males, 40 females) underwent planar radionuclide angiography with 925 MBq 99mTc-ECD. After correction for camera dead-time loss, hemispheric CBF was calculated from brain perfusion indices (BPI): BPI(G) for PGA and BPI(S) for SA. Of the volunteers, 49 also underwent venous sampling 6 min post injection, from which the lipophilic octanol extraction fraction and hemispheric brain fractionation index (BFI) were determined. All datasets were correlated and evaluated as a function of age and gender. Intrasubject variability for the BPI measurements was assessed in 11 volunteers by repeat study within 2 weeks of the first acquisition. Graphical and spectral analysis BPIs were strongly correlated (R=0.846, P<0.00001). This correlation coefficient increased to R=0.903 for the 74 cases in which graphical analysis was not hampered by temporal tracer retention in cervicobrachial venous valves. The BFI was weakly correlated to both BPI indices (BPI(G): R=0.34, P=0.02; BPI(S): R=0.31, P=0.04). The right hemisphere showed significant asymmetry for BPI(S) (AI=2.7%+/-4.3%, P<0.001), in correspondence with previous 99mTc-ECD data. BPI(G), BPI(S) and BFI were all inversely related to age, with an increased gradient after the age of 55 years, while there was no significant gender difference. The ratio of BPI(G) to BIP(S), which is a measure of the cerebral extraction fraction for 99mTc-ECD, was not dependent on age. Intersubject variability was 15.5% for both radionuclide scanning-based methods and 18.2% for venous sampling, and in all cases was independent of age. A much lower intrasubject variability was observed for BPI(S) (7.2%) than for BPI(G) (12.6%). This study provides reference values for normal perfusion indices assessed by graphical and spectral analysis. The results also indicate that spectral analysis allows the most reproducible estimate of hemispheric perfusion by means of an operator-independent and objective approach. Whereas accurate calibration of normal BPI(S) values to hemispheric CBF with established methods needs to be performed, non-invasive calculation of regional absolute CBF using 99mTc-ECD is possible by application of a linearisation algorithm.     

Reference data for 51Cr-EDTA measurements of the glomerular filtration rate derived from live kidney donors

BACKGROUND AND AIM: 51Cr-Ethylenediaminetetraacetic acid (51Cr-EDTA) is widely used to measure the glomerular filtration rate (GFR) for the assessment of renal function. The aims of this study were to assess the dependence of GFR on age and gender and to produce reference data for the interpretation of 51Cr-EDTA GFR measurements in adults. METHODS: This was a retrospective study of 428 subjects (218 females, 210 males; age range, 19-72 years) undergoing assessment as live kidney donors. GFR was evaluated from 51Cr-EDTA plasma clearance using blood samples taken at 2, 3 and 4 h. The slope-intercept GFR was corrected for body surface area using the Haycock formula and for the fast exponential using the Brochner-Mortensen equation. The data were analysed for the dependence on age and gender using multivariate regression analysis. Precision was evaluated from duplicate measurements in 22 subjects. RESULTS: For 187 subjects, aged 19-40 years, the dependence of GFR on age was not statistically significant (P = 0.51). The mean GFR was 103.4 ml x min(-1) x (1.73 m2)(-1) with a root mean standard error (RMSE) of 15.5 ml x min(-1) x (1.73 m2)(-1). GFR was 1.3 ml x min(-1) x (1.73 m2)(-1) higher in men than in women, although the difference was not significant (P = 0.56). In 241 subjects, aged 40-73 years, GFR decreased by 0.91 ml x min(-1) x (1.73 m2)(-1) per year [standard error, 0.06 ml x min(-1) x (1.73 m2)(-1) per year] with an RMSE of 13.6 ml x min(-1) x (1.73 m2)(-1). Over both age groups GFR was 0.4 ml x min(-1) x (1.73 m2)(-1) higher in men than in women [P=0.80; 95% confidence interval, -2.4 to +3.1 ml x min(-1) x (1.73 m2)(-1)]. For the 22 subjects with duplicate measurements, the root mean square coefficient of variation was 10.4%.CONCLUSIONS: A model for the decline of GFR with age was produced in which GFR remains constant at 103.4 ml x min(-1) x (1.73 m2)(-1) until the age of 40 years and then declines at a rate of 9.1 ml x min(-1) x (1.73 m2)(-1) per decade. The data can be used to report the results of adult 51Cr-EDTA GFR investigations.     

Precision of the CASL-perfusion MRI technique for the measurement of cerebral blood flow in whole brain and vascular territories

PURPOSE: To analyze the precision of cerebral blood flow (CBF) measurements made with continuous arterial spin labeling(CASL) perfusion magnetic resonance imaging (MRI) over experimentally relevant intervals. MATERIALS AND METHODS: CASL perfusion MRI measurements of CBF on a 1.5-T GE Signa magnet were repeated in young healthy male and female subjects at one hour and one week. Precision of the measurement was evaluated at both time intervals. RESULTS: CASL perfusion MRI measurements of CBF yielded within-subject coefficients of variation (wsCV) of 5.8% for global and 13% for individual vascular regions when measurements were repeated within one hour. Differences in these values represent the error in post-processing. Global and regional CBF measurements over one week yielded wsCVs of 13% and 14%, respectively. At one week, error secondary to physiologic variability affected global and regional measurements to the same degree and masked the software post-processing error seen at one hour. The magnitude of the difference in repeated measures correlated with the magnitude of the measurement. CONCLUSION: CASL perfusion MRI CBF measurements are accurate and precise. Variability over longer periods of time appears attributable to physiologic factors. Repeatability of the CASL measurement is sensitive to the magnitude of the measurement. This should be taken into account when studies requiring repeated measures involve subjects with significant variability in CBF.     

Automatic semi-quantification of [123I]FP-CIT SPECT scans in healthy volunteers using BasGan version 2: results from the ENC-DAT database

Purpose

The aim of this study was to assess striatal dopamine transporter (DAT) availability in a large group of normal subjects.

Methods

The study included 122 healthy subjects, aged 18–83 years, recruited in the multicentre ‘ENC-DAT’ study (promoted by the European Association of Nuclear Medicine). Brain single photon emission computed tomography (SPECT) was acquired by means of dual-head cameras 3 h after [¹²³I]FP-CIT administration. Specific to nondisplaceable binding ratios (SBRs) in the basal ganglia were computed using the ‘BasGan’ software, allowing automatic value extraction with partial volume effect correction. Multicentre camera inhomogeneity was taken into account by calibrating values on basal ganglia phantom data. SBR in each caudate nucleus (C) and putamen (P) were the dependent variables in a repeated measures general linear model analysis; age, gender, handedness and body mass index (BMI) were the independent variables.

Results

SBR values in C and P were significantly associated with age (mean rate decrease with age: 0.0306 per year, or 0.57 % of the general mean; p?<?0.0001) and gender (women had higher values; p?=?0.015), while no significant effect was found for handedness and BMI. A significant interaction was found between age and region (p?<?0.0001) as the age-related decline was 0.028 for left C, 0.026 for right C and 0.034 for both P. P/C ratio analysis confirmed that age-related SBR decrease was stronger in P than in C (p?<?0.0001). No significant effect was found for season or time of the day when the scan was acquired by analysing the residual of SBR values in C and P, after subtraction of age and gender effects.

Conclusion

This study confirms the dependency of DAT on ageing and highlights the gender differences in a large sample of healthy subjects, while it does not support the dependency of DAT on BMI, handedness, circadian rhythm or season.     

Normal patterns on 99mTc-ECD brain SPECT scans in adults.

Normative ethyl cysteinate dimer (ECD) SPECT data must be available to successfully apply ECD SPECT to clinical studies. The purpose of this study was to determine ECD SPECT scan patterns of healthy adults. METHODS: Forty-eight healthy volunteers (22 men, 26 women; age range, 22-95 y; mean age, 47.6 +/- 19.2 y) underwent high-resolution ECD SPECT. For visual analysis of regional brain ECD uptake, we used a scale of +3 to -3, in which +3 and -3 indicated highest ECD uptake and deficit, respectively. For quantitative analysis, we measured the region-to-cerebellum ratio (R/CE) and the region-to-cerebral cortex ratio (R/CO) for 17 regions (13 cortical, 3 subcortical, and 1 cerebellar). RESULTS: On visual analysis, no subject had a score of -3. All subjects had a score of -2 for the hippocampus and a score of +3 for the medial occipital cortex, except for 2 subjects who had a score of +3 for the striatum and thalamus. A frontal eye field and posterior parieto-occipital junction were identified in 60% of subjects with a score of +1 and 79% of subjects with a score of +2. On quantitative analysis, a significant regional variation (ANOVA, P < 0.0001) was seen in R/CE, ranging from 0.709 (hippocampus) to 1.26 (medial occipital cortex). However, regional right-to-left differences and intersubject variability of R/CE were small (asymmetry index, 3.6% +/- 0.8%; coefficient variation, 6.6% +/- 0.7%). R/CE declined significantly with age in 6 regions, including the anterior and posterior cingulate cortex, superior prefrontal and parietal cortex, striatum, and hippocampus (1.0%-2.0% per decade, P < 0.05), whereas R/CO in the cerebellum increased significantly with age (1.0% per decade, P < 0.05). CONCLUSION: Although regional ECD brain perfusion patterns vary significantly, including variability caused by the age-related effect, intersubject variability is small. Recognition of these normal patterns is important for clinical interpretation of ECD SPECT studies.     

99mTc-ECD brain perfusion SPET: variability, asymmetry and effects of age and gender in healthy adults

Reliable and high-resolution reference data for regional cerebral blood flow measured with single-photon emission tomography (SPET) are necessary for optimal clinical and research use. Therefore, a large dataset of normal technetium-99m labelled ethylene cysteine dimer (ECD) perfusion SPET in carefully screened healthy volunteers with an age range spanning six decades was created, with correction for non-uniform attenuation and scatter and based on an anatomically standardised analysis. Eighty-nine healthy volunteers, stratified for gender (46 females, 43 males; age 20-81 years), were included. Twelve volunteers underwent repeated 99mTc-ECD SPET after 2.5+/-2.3 weeks. An automated whole-brain volume of interest analysis with MANOVA as well as voxelwise analysis using SPM99 was conducted. Average intersubject variability was 4.8% while intrasubject reproducibility was 3.0%. An age-related decline in tracer uptake was found in the anterior cingulate gyrus, bilateral basal ganglia, left prefrontal, left lateral frontal and left superior temporal and insular cortex (all P=0.001-0.02). There was an overall increase in right/left asymmetry with age, which was most pronounced in the frontal and temporal neocortex. The most significant correlations between AI and age decade were found in the prefrontal (R=0.35, P=0.001) and superior temporal neocortex (R=0.43, P<0.001). Women had significantly higher uptake in the right parietal cortex (P<0.001), while men showed higher uptake in the cerebellum and the left anterior temporal and orbitofrontal cortex (all P<0.01). This normative dataset allows age- and gender-specific patient and group assessment of 99mTc-ECD perfusion SPET under a wide variety of clinical circumstances in relation to normal variations and highlights the importance of both age- and gender-specific normal datasets for optimal analysis sensitivity.     

Quantitative cerebral perfusion using dynamic susceptibility contrast MRI: evaluation of reproducibility and age- and gender-dependence with fully automatic image postprocessing algorithm.

A novel approach for quantifying cerebral blood flow (CBF) is proposed that combines the bookend technique of calculating cerebral perfusion with an automatic postprocessing algorithm. The reproducibility of the quantitative CBF (qCBF) measurement in healthy controls (N = 8) showed a higher intraclass correlation coefficient (ICC) and lower coefficient of variation (COV) when calculated with automatic analysis (ICC/COV = 0.90/0.09) than when compared to conventional manual analysis (ICC/COV = 0.58/0.19). Also, the reproducibility in patients (N = 25) was successfully evaluated with the automatic analysis (ICC/COV = 0.81/0.14). In 175 consecutive clinical scans, we found 3.0% and 7.4% of qCBF decrease per decade in white matter (WM) (21.5 +/- 6.66 ml/100 g-min) and gray matter (GM) (49.6 +/- 16.2 ml/100 g-min), respectively. Cerebral blood volume (CBV) showed a significant 3.7% decrease per decade in GM (3.00 +/- 0.94 ml/100 g) but not in WM (1.69 +/- 0.40 ml/100 g). Mean transit time (MTT) increased by 1.9% and 3.8% per decade in WM (5.04 +/- 0.88 s) and GM (4.14 +/- 0.80 s), respectively. qCBF and MTT values between males (N = 85) and females (N = 90) were significantly different in GM. Women showed 11% higher qCBF as well as a higher decrease in qCBF with increasing age than men in the whole brain (WB). Our results supported the notion that population average empirical quantification of cerebral perfusion is subject to individual variation as well as age- and gender-dependent variability.     

Pulmonary blood flow distribution in erect man in air and during breathhold diving

We used intravenously administered 99mTc-labelled macroaggregates and a gamma camera attached to a computer for measuring distribution of pulmonary blood flow per unit lung volume in eight healthy subjects sitting erect in air and also during breathhold diving to 1 or 10 m of depth. We measured distribution of perfusion in the supine position and substituted regional lung volume with regional perfusion in the supine for calculating regional perfusion per lung volume erect in air and during diving. The perfusion per unit lung increased rectilinearly down the lung in subjects below 30 years of age but decreased in the lowermost regions in older subjects. This decrease showed a strong correlation to closing capacity. An age-related decrease in transpulmonary pressure may influence both basal perfusion and closing capacity. During submersion, perfusion became equal in all regions with the exception of the lung apex which became hyperperfused. Close to the diaphragm, small inconsistent changes were noted. Redistribution was the same at surface (1 m of depth) with the lung volume being close to total lung capacity and at 10 m of depth when lung volume was compressed to functional residual capacity. During breathhold diving, high intrapulmonary blood volume and pressure became more important for blood flow distribution than gravity or lung volume, while differences in regional hypoxic vasoconstriction and in transpulmonary pressure seem to explain interindividual variation.     

Prognosis in patients with suspected or known ischemic heart disease and normal myocardial perfusion: Long-term outcome and temporal risk variations

Background

The prognostic value of a normal myocardial perfusion scintigraphy (MPS) may be well described, but long-term follow-up data are sparse, and temporal variations in risk are insufficiently elucidated.

Methods and Results

During long-term follow-up (mean 6.2 years) of 1,327 consecutive Danish patients with normal MPS, the rate of all-cause death (ACD) was 1.9%/year (differing by gender) and of cardiac death (CD)/myocardial infarction (MI) 0.8%/year (differing by coronary artery disease, CAD). Female gender (HR: 0.60), age (HR: 1.07 per-year increment), and known CAD without prior revascularization (HR: 2.17) were statistically significant factors for ACD, whereas diabetes and previous MI per se were not. Known CAD with previous revascularization carried a low risk of ACD when adjusted for gender and age (HR: 0.56). For CD/MI, risk increased with age and threefold with known CAD, previous MI, and previous percutaneous coronary intervention. Judged from smoothed hazard functions, mortality risk increased further with time for men, elderly, and diabetics and markedly further with known CAD without prior revascularization.

Conclusions

Following a normal MPS, rates of death and hard cardiac events were low. Risk varied with age, gender, and disease history. Novel aspects of temporal risk variation suggested a general warranty period of 5 years, but less in risk groups.     

Brain white-matter volume loss and glucose hypometabolism precede the clinical symptoms of Huntington's disease.

We studied the anatomic and functional changes in various brain areas during the course of Huntington's disease (HD) in a large cohort of mutation-positive individuals (n = 71) encompassing the complete range of disability (presymptomatic through stage V), and in healthy controls, for the purpose of defining both degenerative and dysfunctional brain changes in the same subjects. METHODS: We used an MRI and unsupervised multiparametric segmentation procedure based on a relaxometric approach to measure in vivo brain volumes in 71 subjects with presymptomatic to advanced HD. The same population was evaluated by 18F-FDG PET to assess variations in brain glucose metabolism. To predict age at onset in unaffected mutation carriers, we considered the estimated number of years from each subject's age to manifested HD symptoms, for a given expanded triplet number. RESULTS: Age-adjusted analyses confirmed that the 71 subjects as a group, as well as the subgroup of 24 unaffected presymptomatic subjects at risk for HD, had significantly smaller gray-matter and white-matter volumes and larger cerebrospinal fluid volumes than did controls (P < 0.0001). In the 24 presymptomatic subjects, we observed a significant inverse linear correlation between white-matter volume reduction and the estimated time to symptom onset (r2= 0.39; P = 0.0011). Both clinically unaffected subjects at risk for HD and symptomatic patients had significantly decreased glucose uptake in the cortex (frontal and temporal lobes) and striatum (caudate and putamen). HD subjects who were followed up longitudinally showed progressive white-matter reduction in the preclinical subjects (n = 10) and decreased glucose uptake in the cortex and striatum in affected (n = 21) and preclinical (n = 10) subjects. CONCLUSION: White-matter volume loss may precede gray-matter atrophy and may be associated with neuronal dysfunction in early disease.     

Estimation of intersubject variability of cerebral blood flow measurements using MRI and positron emission tomography

Purpose:

To investigate the within and between subject variability of quantitative cerebral blood flow (CBF) measurements in normal subjects using various MRI techniques and positron emission tomography (PET).

Materials and Methods:

Repeated CBF measurements were performed in 17 healthy, young subjects using three different MRI techniques: arterial spin labeling (ASL), dynamic contrast enhanced T1 weighted perfusion MRI (DCE) and phase contrast mapping (PCM). All MRI measurements were performed within the same session. In 10 of the subjects repeated CBF measurements by ¹⁵O labeled water PET had recently been performed. A mixed linear model was used to estimate between subject (CV_betw) and within subject (CV_with) coefficients of variation.

Results:

Mean global CBF, CV_betw and CV_with using each of the four methods were for PCM 65.2 mL/100 g/min, 17.4% and 7.4%, for ASL 37.1 mL/100 g/min, 16.2% and 4.8%, for DCE 43.0 mL/100 g/min, 20.0%, 15.1% and for PET 41.9 mL/100 g/min, 16.5% and 11.9%, respectively. Only for DCE and PCM a significant positive correlation between measurements was demonstrated.

Conclusion:

These findings confirm large between subject variability in CBF measurements, but suggest also that in healthy subjects a subject‐method interaction is a possible source of between subject variability and of method differences. J. Magn. Reson. Imaging 2012;35:1290–1299. © 2012 Wiley Periodicals, Inc.     

Application of MRI-based partial-volume correction to the analysis of PET images of mu-opioid receptors using statistical parametric mapping.

The accurate quantification of brain radioactivity concentration is limited by the spatial resolution of the PET scanner for structures smaller than 2-3 times the resolution. In the presence of enlarged cerebrospinal fluid spaces or regions of cortical neuronal loss, a significant underestimation of gray-matter radioactivity concentration due to the resulting partial-volume averaging can potentially occur. To recover the true radioactivity concentration from PET data, algorithms that use the high-resolution anatomic information provided by MRI have been developed. Their effect on PET quantification has been assessed using regions of interest and non-operator-dependent voxel-based analyses such as statistical parametric mapping (SPM), although the mechanisms that lead to an improvement in PET quantification after partial-volume correction (PVC), compared with no PVC, have not been addressed. METHODS: We studied the influence of our previously described MRI-based PVC algorithm on SPM analysis of age effects on mu-opioid receptor (mu -OR) binding using (11)C-carfentanil PET in 14 healthy subjects (age range, 29-74 y). RESULTS: Mu-OR binding increased with age at a rate of about 0.9% per year in the left temporal cortex after PVC, consistent with the results obtained from human autoradiographic studies. Without PVC, no significant relationship with age was observed. PVC decreased mainly the residual variability of voxel mu-OR binding values around the age regression line. CONCLUSION: MRI-based PVC improves the sensitivity and accuracy of voxel-based statistical analysis of PET data.     

Evaluation of 1H-magnetic resonance spectroscopy of breast cancer pre- and postgadolinium administration

OBJECTIVES: We sought to evaluate spectroscopic measurements in breast cancer and compare variability in choline peak parameters related to contrast administration versus that inherent to repeated measurements. MATERIALS AND METHODS: Single-voxel, proton spectroscopy measurements were obtained before and after the administration of gadolinium on 15 patients with > or = 1-cm breast cancers. The protocol was repeated on a separate day in 7 patients. RESULTS: Postcontrast spectra demonstrated a significant increase in choline peak linewidth (day 1: 15% +/- 21%, P = 0.03; day 2: 19% +/- 12%, P = 0.001) and decrease in choline peak area (day 1: 11% +/- 9% (P < 0.001); day 2: 18% +/- 21% (P = 0.03). A variance-components analysis indicated that day-to-day variation in linewidth accounted for 0.0% of the total variation in width measurements and was not significant (P = 0.85). Day-to-day variation in area was also not significant (0.0%, P = 0.95). CONCLUSIONS: Contrast administration caused significant increases in choline peak linewidth and decreases in choline peak area in spectroscopic measurements of breast cancer.     

Vertebral bone mineral density, marrow perfusion, and fat content in healthy men and men with osteoporosis: dynamic contrast-enhanced MR imaging and MR spectroscopy

PURPOSE: To prospectively use hydrogen 1 (1H) magnetic resonance (MR) spectroscopy and dynamic contrast material-enhanced MR imaging to measure vertebral body marrow fat content and bone marrow perfusion in older men with varying bone mineral densities as documented with dual x-ray absorptiometry (DXA). MATERIALS AND METHODS: This study had institutional review board approval, and all participants provided informed consent. DXA, 1H MR spectroscopy, and dynamic contrast-enhanced MR imaging of the lumbar spine were performed in 90 men (mean age, 73 years; range, 67-101 years). Vertebral marrow fat content and perfusion (maximum enhancement and enhancement slope) were compared for subject groups with differing bone densities (normal, osteopenic, and osteoporotic). The t test was used for comparisons between groups, and the Pearson test was used to determine correlation between marrow fat content and perfusion indexes. RESULTS: Eight subjects were excluded, yielding a final cohort of 82 subjects (mean age, 73 years; range, 67-101 years) that included 42 subjects with normal bone density (mean T score, 0.8 +/- 1.1 [standard deviation]), 23 subjects with osteopenia (mean T score, -1.6 +/- 0.4), and 17 subjects with osteoporosis (mean T score, -3.2 +/- 0.5). Vertebral marrow fat content was significantly increased in subjects with osteoporosis (mean fat content, 58.23% +/- 7.8) (P = .002) or osteopenia (mean fat content, 55.68% +/- 10.2) (P = .034) compared with that in subjects with normal bone density (50.45% +/- 8.7). Vertebral marrow perfusion indexes were significantly decreased in osteoporotic subjects (mean enhancement slope, 0.78%/sec +/- 0.3) compared with those in osteopenic subjects (mean enhancement slope, 1.15%/sec +/- 0.6) (P = .007) and those in subjects with normal bone density (mean enhancement slope, 1.48%/sec +/- 0.7) (P < .001). CONCLUSION: Subjects with osteoporosis have decreased vertebral marrow perfusion and increased marrow fat compared with these parameters in subjects with osteopenia. Similarly, subjects with osteopenia have decreased vertebral marrow perfusion and increased marrow fat compared with these parameters in subjects with normal bone density.     

Multisite fMRI reproducibility of a motor task using identical MR systems

PURPOSE: To estimate between-scanner functional MRI (fMRI) reproducibility in a multisite study. MATERIALS AND METHODS: A total of five identical 1.5T MR systems were used to repeatedly scan five subjects while performing a finger tapping task. A two-way (scanners, subjects) random effects analysis of variance (ANOVA) was used to estimate between-scanner and between-subject variability on two outcome variables: task-related mean blood oxygenation level dependent (BOLD) signal change and volume of activation within a motor region-of-interest (ROI). RESULTS: Between-scanner variability of fMRI data accounted for a small proportion of the total variation in the BOLD signal change (8.34%, P = 0.114) and volume of activation (5.46%, P = 0.203). Between-subject variation accounted for more than half of the total variation for both measurements (57.17% and 54.46%, respectively, P < 0.01). CONCLUSION: These results support the feasibility of multisite studies using identical scanner systems.     

A quantitative approach to technetium-99m hexamethylpropylene amine oxime.

A non-invasive, simple method for the quantitative evaluation of brain perfusion is presented using intravenous radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTc-HM-PAO). Graphical analysis was employed for the evaluation of the unidirectional influx constant (ku) of the tracer from the blood to the brain. The ku values were standardized to provide objective and comparable values, brain perfusion indices (BPI), among studied subjects by setting the ratio of ROIbrain size to ROIaorta size at 10. The whole-brain BPI values for the normal control subjects showed a significant negative correlation with advancing age (r = -0.632, P = 0.0204, n = 13). The mean of the whole-brain BPI of 7.0 (SD = 1.4) in 20 patients with cerebrovascular disorders was significantly lower than that of 10.6 (SD = 1.5) in 13 normal control subjects. The BPI measurements showed only minimal intra- and interobserver variability. Changes of the ratio of ROIaorta size and ROIbrain size did not significantly influence the BPI values. Hemispherical BPI values in 19 subjects (n = 38) showed highly significant correlations with the hemispherical mean cerebral blood flow values obtained from Xenon-133 single photon emission tomography (SPET) (r = 0.926, P = 0.0001 for the early picture method and r = 0.932, P = 0.0001 for the sequential picture method). This technique is easy to apply as an adjunct to SPET and may be helpful in the quantitative evaluation of brain perfusion in routine clinical studies.     

Regional cerebral blood flow as assessed by principal component analysis and <Superscript>99m</Superscript>Tc-HMPAO SPET in healthy subjects at rest: normal distribution and effect of age and gender

The increasing implementation of standardisation techniques in brain research and clinical diagnosis has highlighted the importance of reliable baseline data from normal control subjects for inter-subject analysis. In this context, knowledge of the regional cerebral blood flow (rCBF) distribution in normal ageing is a factor of the utmost importance. In the present study, rCBF was investigated in 50 healthy volunteers (25 men, 25 women), aged 31-78 years, who were examined at rest by means of single-photon emission tomography (SPET) using technetium-99m d, l-hexamethylpropylene amine oxime (HMPAO). After normalising the CBF data, 27 left and 27 right volumes of interest (VOIs) were selected and automatically outlined by standardisation software (computerised brain atlas). The heavy load of flow data thus obtained was reduced in number and grouped in factors by means of principal component analysis (PCA). PCA extracted 12 components explaining 81% of the variance and including the vast majority of cortical and subcortical regions. Analysis of variance and regression analyses were performed for rCBF, age and gender before PCA was applied and subsequently for each single extracted factor. There was a significantly higher CBF on the right side than on the left side ( P<0.001). In the overall analysis, a significant decrease was found in CBF ( P=0.05) with increasing age, and this decrease was particularly evident in the left hemisphere ( P=0.006). When gender was specifically analysed, CBF was found to decrease significantly with increasing age in females ( P=0.037) but not in males. Furthermore, a significant decrease in rCBF with increasing age was found in the brain vertex ( P=0.05), left frontotemporal cortex ( P=0.012) and temporocingulate cortex ( P=0.003). By contrast, relative rCBF in central structures increased with age ( P=0.001). The ability of standardisation software and PCA to identify functionally connected brain regions might contribute to a better understanding of the relationships between rCBF at rest, anatomically defined brain structures, ageing and gender.     

Functional evaluation of transplanted kidneys with diffusion-weighted and BOLD MR imaging: initial experience

PURPOSE: To prospectively evaluate feasibility and reproducibility of diffusion-weighted (DW) and blood oxygenation level-dependent (BOLD) magnetic resonance (MR) imaging in patients with renal allografts, as compared with these features in healthy volunteers with native kidneys. MATERIALS AND METHODS: The local ethics committee approved the study protocol; patients provided written informed consent. Fifteen patients with a renal allograft and in stable condition (nine men, six women; age range, 20-67 years) and 15 age- and sex-matched healthy volunteers underwent DW and BOLD MR imaging. Seven patients with renal allografts were examined twice to assess reproducibility of results. DW MR imaging yielded a total apparent diffusion coefficient including diffusion and microperfusion (ADC(tot)), as well as an ADC reflecting predominantly pure diffusion (ADC(D)) and the perfusion fraction. R2* of BOLD MR imaging enabled the estimation of renal oxygenation. Statistical analysis was performed, and analysis of variance was used for repeated measurements. Coefficients of variation between and within subjects were calculated to assess reproducibility. RESULTS: In patients, ADC(tot), ADC(D), and perfusion fraction were similar in the cortex and medulla. In volunteers, values in the medulla were similar to those in the cortex and medulla of patients; however, values in the cortex were higher than those in the medulla (P < .05). Medullary R2* was higher than cortical R2* in patients (12.9 sec(-1) +/- 2.1 [standard deviation] vs 11.0 sec(-1) +/- 0.6, P < .007) and volunteers (15.3 sec(-1) +/- 1.1 vs 11.5 sec(-1) +/- 0.5, P < .0001). However, medullary R2* was lower in patients than in volunteers (P < .004). Increased medullary R2* was paralleled by decreased diffusion in patients with allografts. A low coefficient of variation in the cortex and medulla within subjects was obtained for ADC(tot), ADC(D), and R2* (<5.2%), while coefficient of variation within subjects was higher for perfusion fraction (medulla, 15.1%; cortex, 8.6%). Diffusion and perfusion indexes correlated significantly with serum creatinine concentrations. CONCLUSION: DW and BOLD MR imaging are feasible and reproducible in patients with renal allografts.     

Normal biventricular function,volumes, and mass in children aged 8 to 17 years

Purpose

To assess normal values for biventricular function, volumes, and mass with current cardiovascular magnetic resonance (CMR) imaging sequences in children.

Materials and Methods

Included in the study were 60 healthy children aged 8–17 years. A short axis set of contiguous slices was acquired with CMR imaging employing steady‐state free precession. Biventricular end‐diastolic volume (EDV), end‐systolic volume (ESV), ejection fraction (EF), and mass were determined. Uni‐ and multivariate linear regression analyses were performed to study the interrelation of age, gender, and body surface area (BSA) on biventricular volumes and mass. The coefficient of variation was calculated for intra‐ and interobserver variability.

Results

EF did not differ between boys and girls (mean LV‐EF 69 ± (SD) 5%, mean RV‐EF 65 ± 5%). BSA had good (EDV, mass) and modest (ESV) correlation with biventricular measurements. Gender appeared a significant modifier of these relations, whereas age had no independent contribution. The intra‐ and interobserver coefficient of variation was in the range 2.1%–13.9% for biventricular EDV, ESV, and mass.

Conclusion

This study reveals gender‐specific normative data for biventricular function, volumes, and mass in children age 8–17 years that can be used as reference data in the follow‐up of pediatric cardiac patients. J. Magn. Reson. Imaging 2009;29:552–559. © 2009 Wiley‐Liss, Inc.     

Evidence for exercise-induced bone formation in premature infants

We assessed the effect of a four weeks exercise training intervention on bone turnover markers in premature infants. Twenty-four very low birth weight premature infants were matched for gestational age, birth weight, gender, as well as for corrected age and weight at initiation of the study. Then the subjects were randomly divided into an exercise (n = 12) and a control group (n = 12). Exercise consisted of passive range of motion exercise with gentle compression of both the upper and lower extremities lasting 5 - 10 minutes each day, 5 days per week for 4 weeks. This protocol has been shown to increase bone mineral density in premature infants. Bone formation was assessed by measurements of circulating bone specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP). Bone resorption was determined by serum measurements of C- terminal cross-links telopeptide of type-I collagen (ICTP). Training led to a significant (P < 0.05) increase in weight gain (767 +/- 49 versus 586 +/- 24 gr in trained and control premature infants, respectively); and to a significant increase in BSAP (37.2 +/- 14.6 versus 4.1 +/- 8.4 % in trained and control premature infants, respectively). PICP increased also following exercise (34.6 +/- 18.9 versus 5.4 +/- 9.1 % in trained and control subjects, respectively), however, this increase was not statistically significant. Exercise led to a significant decrease in ICTP (-24.7 +/- 3.1 versus -5.5 +/- 5.4 % in trained and control subjects, respectively). A relatively brief exercise intervention was associated with a biochemical evidence of bone formation in very low birth weight premature infants.