Samuel Patz

25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services

Background: Vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. However, no studies have examined the association between vitamin D status, dementia, and cranial MRI indicators of cerebrovascular disease (CVD). Methods: Cross-sectional investigation of 25-hydroxyvitamin D [25(OH)D], dementia, and MRI measures of CVD in elders receiving home care (aged 65–99 years) from 2003 to 2007. Results: Among 318 participants, the mean age was 73.5 ± 8.1 years, 231 (72.6%) were women, and 109 (34.3%) were black. 25(OH)D concentrations were deficient (<10 ng/mL) in 14.5% and insufficient (10–20 ng/mL) in 44.3% of participants. There were 76 participants (23.9%) with dementia, 41 of which were classified as probable AD. Mean 25(OH)D concentrations were lower in subjects with dementia (16.8 vs 20.0 ng/mL, p < 0.01). There was a higher prevalence of dementia among participants with 25(OH)D insufficiency (≤20 ng/mL) (30.5% vs 14.5%, p < 0.01). 25(OH)D deficiency was associated with increased white matter hyperintensity volume (4.9 vs 2.9 mL, p < 0.01), grade (3.0 vs 2.2, p = 0.04), and prevalence of large vessel infarcts (10.1% vs 6.9%, p < 0.01). After adjustment for age, race, sex, body mass index, and education, 25(OH)D insufficiency (≤20 ng/mL) was associated with more than twice the odds of all-cause dementia (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.2–4.2), Alzheimer disease (OR = 2.5, 95% CI 1.1–6.1), and stroke (with and without dementia symptoms) (OR = 2.0, 95% CI 1.0–4.0). Conclusions: Vitamin D insufficiency and deficiency was associated with all-cause dementia, Alzheimer disease, stroke (with and without dementia symptoms), and MRI indicators of cerebrovascular disease. These findings suggest a potential vasculoprotective role of vitamin D.

Evidence for Adult Lung Growth in Humans

A 33-year-old woman underwent a right-sided pneumonectomy in 1995 for treatment of a lung adenocarcinoma. As expected, there was an abrupt decrease in her vital capacity, but unexpectedly, it increased during the subsequent 15 years. Serial computed tomographic (CT) scans showed progressive enlargement of the remaining left lung and an increase in tissue density. Magnetic resonance imaging (MRI) with the use of hyperpolarized helium-3 gas showed overall acinar-airway dimensions that were consistent with an increase in the alveolar number rather than the enlargement of existing alveoli, but the alveoli in the growing lung were shallower than in normal lungs. This study provides evidence that new lung growth can occur in an adult human.

Near-unity nuclear polarization with an open-source 129Xe hyperpolarizer for NMR and MRI

Significance Lung diseases comprise the third leading cause of death in the United States and could benefit from new imaging modalities. “Hyperpolarized” xenon-129 can overcome the ordinarily weak MRI signals from low-density species in lung space or dissolved in tissue; however, clinical progress has been slowed by the difficulty in preparing large amounts of hyperpolarized xenon with high magnetization, as well as the cost and limited availability of xenon hyperpolarization devices. We describe a unique low-cost “open-source” xenon “hyperpolarizer,” characterize its ability to produce xenon-129 with high magnetization, and demonstrate its utility for human lung imaging. The exquisite NMR spectral sensitivity and negligible reactivity of hyperpolarized xenon-129 (HP129Xe) make it attractive for a number of magnetic resonance applications; moreover, HP129Xe embodies an alternative to rare and nonrenewable 3He. However, the ability to reliably and inexpensively produce large quantities of HP129Xe with sufficiently high 129Xe nuclear spin polarization (PXe) remains a significant challenge—particularly at high Xe densities. We present results from our “open-source” large-scale (∼1 L/h) 129Xe polarizer for clinical, preclinical, and materials NMR and MRI research. Automated and composed mostly of off-the-shelf components, this “hyperpolarizer” is designed to be readily implementable in other laboratories. The device runs with high resonant photon flux (up to 200 W at the Rb D1 line) in the xenon-rich regime (up to 1,800 torr Xe in 500 cc) in either single-batch or stopped-flow mode, negating in part the usual requirement of Xe cryocollection. Excellent agreement is observed among four independent methods used to measure spin polarization. In-cell PXe values of ∼90%, ∼57%, ∼50%, and ∼30% have been measured for Xe loadings of ∼300, ∼500, ∼760, and ∼1,570 torr, respectively. PXe values of ∼41% and ∼28% (with ∼760 and ∼1,545 torr Xe loadings) have been measured after transfer to Tedlar bags and transport to a clinical 3 T scanner for MR imaging, including demonstration of lung MRI with a healthy human subject. Long “in-bag” 129Xe polarization decay times have been measured (T1 ∼38 min and ∼5.9 h at ∼1.5 mT and 3 T, respectively)—more than sufficient for a variety of applications.

Human pulmonary imaging and spectroscopy with hyperpolarized 129Xe at 0.2T.

RATIONALE AND OBJECTIVES Using a novel (129)Xe polarizer with high throughput (1-2 L/hour) and high polarization (approximately 55%), our objective was to demonstrate and characterize human pulmonary applications at 0.2T. Specifically, we investigated the ability of (129)Xe to measure the alveolar surface area per unit volume of gas, S(A)/V(gas). MATERIALS AND METHODS Variable spin echo time (TE) gradient and radiofrequency (RF) echoes were used to obtain estimates of the lungs contribution to both T(2)* and T(2). Standard multislice ventilation images were obtained and signal-to-noise ratio (SNR) determined. Whole-lung, time-dependent measurements of (129)Xe diffusion from gas to septal tissue were obtained with a chemical shift saturation recovery (CSSR) method. Four healthy subjects were studied, and the Butler et al CSSR formalism (J Phys Condensed Matter 2002; 14:L297-L304) was used to calculate S(A)/V(gas). A single-breath version of the xenon transfer contrast (SB-XTC) method was implemented and used to image (129)Xe diffusion between alveolar gas and septal tissue. A direct comparison of CSSR and SB-XTC was performed. RESULTS T(2)*=135+/-29 ms amd T(2)=326.2+/-9.5 ms. Maximum SNR=36 for ventilation images from inhalation of 1L 86% (129)Xe and voxel volume =0.225 mL. CSSR analysis showed S(A)/V(gas) decreased with increasing lung volume in a manner very similar to that observed from histology measurements; however, the absolute value of S(A)/V(gas) was approximately 40% smaller than histology values. SB-XTC images in different postures demonstrate gravitationally dependent values. Initial comparison of CSSR with XTC showed fairly good agreement with expected ratios. CONCLUSIONS Hyperpolarized (129)Xe human imaging and spectroscopy are very promising methods to provide functional information about the lung.

Large Production System for Hyperpolarized 129Xe for Human Lung Imaging Studies

RATIONALE AND OBJECTIVES Hyperpolarized gases such as (129)Xe and (3)He have high potential as imaging agents for functional lung magnetic resonance imaging (MRI). We present new technology offering (129)Xe production rates with order-of-magnitude improvement over existing systems, to liter per hour at 50% polarization. Human lung imaging studies with xenon, initially limited by the modest quantity and quality of hyperpolarized gas available, can now be performed with multiliter quantities several times daily. MATERIALS AND METHODS The polarizer is a continuous-flow system capable of producing large quantities of highly-polarized (129)Xe through rubidium spin-exchange optical pumping. The low-pressure, high-velocity operating regime takes advantage of the enhancement in the spin exchange rate provided by van der Waals molecules dominating the atomic interactions. The long polarizing column moves the flow of the gas opposite to the laser direction, allowing efficient extraction of the laser light. Separate sections of the system assure full rubidium vapor saturation and removal. RESULTS The system is capable of producing 64% polarization at 0.3 L/hour Xe production rate. Increasing xenon flow reduces output polarization. Xenon polarization was studied as a function of different system operating parameters. A novel xenon trapping design was demonstrated to allow full recovery of the xenon polarization after the freeze-thaw cycle. Delivery methods of the gas to an offsite MRI facility were demonstrated in both frozen and gas states. CONCLUSIONS We demonstrated a new concept for producing large quantities of highly polarized xenon. The system is operating in an MRI facility producing liters of hyperpolarized gas for human lung imaging studies.

Diffusion Tensor Imaging, White Matter Lesions, the Corpus Callosum, and Gait in the Elderly

Background and Purpose— Gait impairment is common in the elderly, especially those with stroke and white matter hyperintensities on conventional brain MRI. Diffusion tensor imaging (DTI) is more sensitive to white matter damage than conventional MRI. The relationship between DTI measures and gait has not been previously evaluated. Our purpose was to investigate the relationship between the integrity of white matter in the corpus callosum as determined by DTI and quantitative measures of gait in the elderly. Methods— One hundred seventy-three participants of a community-dwelling elderly cohort had neurological and neuropsychological examinations and brain MRI. Gait function was measured by Tinetti gait (0 to 12), balance (0 to 16) and total (0 to 28) scores. DTI assessed fractional anisotropy in the genu and splenium of the corpus callosum. Conventional MRI was used to evaluate for brain infarcts and white matter hyperintensity volume. Results— Participants with abnormal gait had low fractional anisotropy in the genu of the corpus callosum but not the splenium. Multiple regressions analyses showed an independent association between these genu abnormalities and all 3 Tinetti scores (P<0.001). This association remained significant after adding MRI infarcts and white matter hyperintensity volume to the analysis. Conclusions— The independent association between quantitative measures of gait function and DTI findings shows that white matter integrity in the genu of corpus callosum is an important marker of gait in the elderly. DTI analyses of white matter tracts in the brain and spinal cord may improve knowledge about the pathophysiology of gait impairment and help target clinical interventions.

Prototype miniature endoluminal MR imaging catheter.

PURPOSE The feasibility of a miniature endoluminal magnetic resonance (MR) detection coil was investigated for imaging mural and perimural anatomy of small, tubular structures. MATERIALS AND METHODS To this end, remotely tunable, single-loop, multiturn, receive-only radio-frequency coils, housed in 6-9-F arterial sheaths, were built. A 1.9-T imager was used. Phantom excitation was accomplished with a 62-mm-diameter bird-cage quadrature coil, and ex vivo specimen excitation was accomplished with a single-turn, untuned wire loop. Phantom images obtained with use of a 9-F catheter coil showed a signal-to-noise improvement on the border of 20 dB compared with images obtained with the quadrature coil. An 8-F catheter coil was used to obtain high-resolution (100 microns in-plane pixel size, 500 microns section thickness) spin-echo images (repetition time = 2,400 msec, echo time = 53 msec) of the wall of a fresh ex vivo human popliteal artery. RESULTS Prospectively, these images were suggestive of the presence of diffuse intimal hyperplasia, medial calcification, and focal atherosclerotic plaque. These findings were confirmed histologically. Three-dimensional restacking of the axial images simplified examination of the normal layers and pathologic changes within the wall. The improved signal-to-noise characteristics of these miniature coils permit fast high-resolution imaging, allowing visualization of microscopic anatomic details. CONCLUSIONS With further development, this technology may be useful for studying atherosclerosis and for providing imaging guidance during endoluminal MR interventions.

Some factors that influence the steady state in steady-state free precession

Steady-state free precession (SSFP) and particularly the spatially periodic magnetization response with wavelength lambda that results in the presence of an applied gradient is discussed. The maximum SSFP magnetization does not always occur at the Larmor frequency but rather depends on both the phase cycling of the rf pulses and on the rf tip angle. The slow flow sensitivity of SSFP also depends on lambda. Experimental data of the flow sensitivity is shown to be parameterized by a dimensionless dephasing parameter phi defined as the ratio of the distance traveled by a spin in one cycle of the SSFP sequence as compared to lambda. An example of the creation of a moving reference frame with the SSFP sequence is given. The modulation in image intensity that results when the gradients are nearly but not exactly compensated and lambda becomes large (i.e., tens of pixels long) is demonstrated. The pixel length must be an integral number of lambdas in order to have a uniform image intensity from a uniform phantom.

Quantitative CT Measurement of Cross-sectional Area of Small Pulmonary Vessel in COPD: Correlations with Emphysema and Airflow Limitation

RATIONALE AND OBJECTIVES Pulmonary vascular alteration is one of the characteristic features of chronic obstructive pulmonary disease (COPD). Recent studies suggest that vascular alteration is closely related to endothelial dysfunction and may be further influenced by emphysema. However, the relationship between morphological alteration of small pulmonary vessels and the extent of emphysema has not been assessed in vivo. The objectives of this study are: to evaluate the correlation of total cross-sectional area (CSA) of small pulmonary vessels with the extent of emphysema and airflow obstruction using CT scans and to assess the difference of total CSA between COPD phenotypes. MATERIALS AND METHODS We measured CSA less than 5 mm(2) and 5-10 mm(2), and calculated the percentage of the total CSA for the lung area (%CSA < 5, and %CSA5-10, respectively) using CT scans in 191 subjects. The extent of emphysema (%LAA-950) was calculated, and the correlations of %CSA < 5 and %CSA5-10 with %LAA-950 and results of pulmonary function tests (PFTs) were evaluated. The differences in %CSA between COPD phenotypes were also assessed. RESULTS The %CSA < 5 had significant negative correlations with %LAA-950 (r = -0.83, P < .0001). There was a weak but statistically significant correlation of %CSA < 5 with forced expiratory volume in 1 second (FEV1)% predicted (r = 0.29, P < .0001) and FEV1/forced vital capacity (r = 0.45, P < .0001). A %CSA 5-10 had weak correlations with %LAA-950 and results of PFTs. %CSA < 5 was significantly higher in bronchitis phenotype than in the emphysema phenotype (P < .0001). CONCLUSIONS Total CSA of small pulmonary vessels at sub-subsegmental levels strongly correlates with the extent of emphysema (%LAA-950) and reflects differences between COPD phenotypes.

Diffusion of hyperpolarized 129Xe in the lung: a simplified model of 129Xe septal uptake and experimental results

We used hyperpolarized 129Xe NMR to measure pulmonary alveolar surface area per unit gas volume SA/Vgas, alveolar septal thickness h and capillary transit time ?, three critical determinants of the lungs primary role as a gas exchange organ. An analytical solution for a simplified diffusion model is described, together with a modification of the xenon transfer contrast imaging technique utilizing 90? radio-frequency pulses applied to the dissolved phase, rather than traditional 180? pulses. With this approach, three-dimensional (3D) maps of SA/Vgas were obtained. We measured global SA/Vgas, h and ? in four normal subjects, two subjects with mild interstitial lung disease (ILD) and two subjects with mild chronic obstructive pulmonary disease (COPD). In normals, SA/Vgas decreased with increasing lung volume from ~320 to 80?cm?1; both h~13??m and ?~1.5?s were relatively constant. For the two ILD subjects, h was, respectively, 36 and 97% larger than normal, quantifying an increased gas/blood tissue barrier; SA/Vgas and ? were normal. The two COPD subjects had SA/Vgas values ~25% that of normals, quantifying septal surface loss in emphysema; h and ? were normal. These are the first noninvasive, non-radiation-based, quantitative measurements of h and ? in patients with pulmonary disease.