MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

BACKGROUND: Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. METHODS: This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS: Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ±â€…13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon corrected Akaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). CONCLUSION: After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Despite advances in medical therapy, many patients with ileal Crohn's disease progress to fibrostenosis requiring surgery. Our study has shown that GM-CSF autoantibodies and MRI biomarker sequences are associated with the need for ileal resection and may help guide management decisions.

The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease.

ABSTRACT: Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin-labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI-measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.

Diagnostic Excellence in Pediatric Spine Imaging: Using Contextualized Imaging Protocols.

Contextual design and selection of MRI protocols is critical for making an accurate diagnosis given the wide variety of clinical indications for spine imaging in children. Here, we describe our pediatric spine imaging protocols in detail, tailored to specific clinical questions.

Study protocol for a randomized, controlled trial using a novel, family-centered diet treatment to prevent nonalcoholic fatty liver disease in Hispanic children.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the leading liver disorder among U.S. children and is most prevalent among Hispanic children with obesity. Previous research has shown that reducing the consumption of free sugars (added sugars + naturally occurring sugars in fruit juice) can reverse liver steatosis in adolescents with NAFLD. This study aims to determine if a low-free sugar diet (LFSD) can prevent liver fat accumulation and NAFLD in high-risk children. METHODS: In this randomized controlled trial, we will enroll 140 Hispanic children aged 6 to 9 years who are ≥50th percentile BMI and without a previous diagnosis of NAFLD. Participants will be randomly assigned to either an experimental (LFSD) or a control (usual diet + educational materials) group. The one-year intervention includes removal of foods high in free sugars from the home at baseline, provision of LFSD household groceries for the entire family (weeks 1-4, 12, 24, and 36), dietitian-guided family grocery shopping sessions (weeks 12, 24, and 36), and ongoing education and motivational interviewing to promote LFSD. Both groups complete assessment measures at baseline, 6, 12, 18, and 24 months. Primary study outcomes are percent hepatic fat at 12 months and incidence of clinically significant hepatic steatosis (>5%) + elevated liver enzymes at 24 months. Secondary outcomes include metabolic markers potentially mediating or moderating NAFLD pathogenesis. DISCUSSION: This protocol describes the rationale, eligibility criteria, recruitment strategies, analysis plan as well as a novel dietary intervention design. Study results will inform future dietary guidelines for pediatric NAFLD prevention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05292352.

Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease.

BACKGROUNDHepatic de novo lipogenesis (DNL) is elevated in nonalcoholic fatty liver disease (NAFLD). Improvements in hepatic fat by dietary sugar reduction may be mediated by reduced DNL, but data are limited, especially in children. We examined the effects of 8 weeks of dietary sugar restriction on hepatic DNL in adolescents with NAFLD and correlations between DNL and other metabolic outcomes.METHODSAdolescent boys with NAFLD (n = 29) participated in an 8-week, randomized controlled trial comparing a diet low in free sugars versus their usual diet. Hepatic DNL was measured as percentage contribution to plasma triglyceride palmitate using a 7-day metabolic labeling protocol with heavy water. Hepatic fat was measured by magnetic resonance imaging-proton density fat fraction.RESULTSHepatic DNL was significantly decreased in the treatment group (from 34.6% to 24.1%) versus the control group (33.9% to 34.6%) (adjusted week 8 mean difference: -10.6% [95% CI: -19.1%, -2.0%]), which was paralleled by greater decreases in hepatic fat (25.5% to 17.9% vs. 19.5% to 18.8%) and fasting insulin (44.3 to 34.7 vs. 35.5 to 37.0 µIU/mL). Percentage change in DNL during the intervention correlated significantly with changes in free-sugar intake (r = 0.48, P = 0.011), insulin (r = 0.40, P = 0.047), and alanine aminotransferase (ALT) (r = 0.39, P = 0.049), but not hepatic fat (r = 0.13, P = 0.532).CONCLUSIONOur results suggest that dietary sugar restriction reduces hepatic DNL and fasting insulin, in addition to reductions in hepatic fat and ALT, among adolescents with NAFLD. These results are consistent with the hypothesis that hepatic DNL is a critical metabolic abnormality linking dietary sugar and NAFLD.TRIAL REGISTRYClinicalTrials.gov NCT02513121.FUNDINGThe Nutrition Science Initiative (made possible by gifts from the Laura and John Arnold Foundation, Ambrose Monell Foundation, and individual donors), the UCSD Altman Clinical and Translational Research Institute, the NIH, Children's Healthcare of Atlanta and Emory University's Children's Clinical and Translational Discovery Core, Children's Healthcare of Atlanta and Emory University Pediatric Biostatistical Core, the Georgia Clinical and Translational Science Alliance, and the NIH National Institute of Diabetes, Digestive, and Kidney Disease.

Development of a Plasma Screening Panel for Pediatric Nonalcoholic Fatty Liver Disease Using Metabolomics.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children, but diagnosis is challenging due to limited availability of noninvasive biomarkers. Machine learning applied to high-resolution metabolomics and clinical phenotype data offers a novel framework for developing a NAFLD screening panel in youth. Here, untargeted metabolomics by liquid chromatography-mass spectrometry was performed on plasma samples from a combined cross-sectional sample of children and adolescents ages 2-25 years old with NAFLD (n = 222) and without NAFLD (n = 337), confirmed by liver biopsy or magnetic resonance imaging. Anthropometrics, blood lipids, liver enzymes, and glucose and insulin metabolism were also assessed. A machine learning approach was applied to the metabolomics and clinical phenotype data sets, which were split into training and test sets, and included dimension reduction, feature selection, and classification model development. The selected metabolite features were the amino acids serine, leucine/isoleucine, and tryptophan; three putatively annotated compounds (dihydrothymine and two phospholipids); and two unknowns. The selected clinical phenotype variables were waist circumference, whole-body insulin sensitivity index (WBISI) based on the oral glucose tolerance test, and blood triglycerides. The highest performing classification model was random forest, which had an area under the receiver operating characteristic curve (AUROC) of 0.94, sensitivity of 73%, and specificity of 97% for detecting NAFLD cases. A second classification model was developed using the homeostasis model assessment of insulin resistance substituted for the WBISI. Similarly, the highest performing classification model was random forest, which had an AUROC of 0.92, sensitivity of 73%, and specificity of 94%. Conclusion: The identified screening panel consisting of both metabolomics and clinical features has promising potential for screening for NAFLD in youth. Further development of this panel and independent validation testing in other cohorts are warranted.

Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A Randomized Clinical Trial.

Importance: Pediatric guidelines for the management of nonalcoholic fatty liver disease (NAFLD) recommend a healthy diet as treatment. Reduction of sugary foods and beverages is a plausible but unproven treatment. Objective: To determine the effects of a diet low in free sugars (those sugars added to foods and beverages and occurring naturally in fruit juices) in adolescent boys with NAFLD. Design, Setting, and Participants: An open-label, 8-week randomized clinical trial of adolescent boys aged 11 to 16 years with histologically diagnosed NAFLD and evidence of active disease (hepatic steatosis >10% and alanine aminotransferase level ≥45 U/L) randomized 1:1 to an intervention diet group or usual diet group at 2 US academic clinical research centers from August 2015 to July 2017; final date of follow-up was September 2017. Interventions: The intervention diet consisted of individualized menu planning and provision of study meals for the entire household to restrict free sugar intake to less than 3% of daily calories for 8 weeks. Twice-weekly telephone calls assessed diet adherence. Usual diet participants consumed their regular diet. Main Outcomes and Measures: The primary outcome was change in hepatic steatosis estimated by magnetic resonance imaging proton density fat fraction measurement between baseline and 8 weeks. The minimal clinically important difference was assumed to be 4%. There were 12 secondary outcomes, including change in alanine aminotransferase level and diet adherence. Results: Forty adolescent boys were randomly assigned to either the intervention diet group or the usual diet group (20 per group; mean [SD] age, 13.0 [1.9] years; most were Hispanic [95%]) and all completed the trial. The mean decrease in hepatic steatosis from baseline to week 8 was significantly greater for the intervention diet group (25% to 17%) vs the usual diet group (21% to 20%) and the adjusted week 8 mean difference was -6.23% (95% CI, -9.45% to -3.02%; P < .001). Of the 12 prespecified secondary outcomes, 7 were null and 5 were statistically significant including alanine aminotransferase level and diet adherence. The geometric mean decrease in alanine aminotransferase level from baseline to 8 weeks was significantly greater for the intervention diet group (103 U/L to 61 U/L) vs the usual diet group (82 U/L to 75 U/L) and the adjusted ratio of the geometric means at week 8 was 0.65 U/L (95% CI, 0.53 to 0.81 U/L; P < .001). Adherence to the diet was high in the intervention diet group (18 of 20 reported intake of <3% of calories from free sugar during the intervention). There were no adverse events related to participation in the study. Conclusions and Relevance: In this study of adolescent boys with NAFLD, 8 weeks of provision of a diet low in free sugar content compared with usual diet resulted in significant improvement in hepatic steatosis. However, these findings should be considered preliminary and further research is required to assess long-term and clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02513121.

Effect of repetition time on metabolite quantification in the human brain in 1 H MR spectroscopy at 3 tesla.

PURPOSE: To examine the effects of repetition time (TR) on metabolite concentration measurements in the human brain in 1 H magnetic resonance spectroscopy at 3 Tesla (T). MATERIALS AND METHODS: Spectra were acquired from the posterior cingulate of five healthy adults at repetition times of 1.5 s, 3.0 s, 4.0 s, 6.0 s, and 8.0 s on a 3T MRI system. Relaxation data were also acquired for the water signal in the voxel of interest to separate tissue water and cerebrospinal fluid signal contributions. All data were quantified relative to total creatine and relative to the tissue water signal. RESULTS: On average, the variance for absolute metabolite concentrations was smaller than that of ratio concentrations (P = 0.003). Metabolite ratio concentrations calculated from a short TR of 1.5 s significantly differed (P < 0.05) from their "true" ratios, i.e., ratios corrected for T1 -weighting. In comparison, absolute metabolite concentrations exhibited significant differences (P < 0.05) up to a 4-s TR. CONCLUSION: To minimize potential TR-dependent concentration differences at 3T, a minimum TR of 2.5 s is suggested for ratio concentration measurements, and a 5-s TR for absolute concentrations. When possible, preference should be to perform absolute concentration measurements. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:710-721.

Very short echo time improves the precision of glutamate detection at 3T in 1H magnetic resonance spectroscopy.

PURPOSE: To examine the precision of glutamate detection using a very short echo time (TE) phase rotation STEAM (PR-STEAM) sequence. MATERIALS AND METHODS: Spectrosopic data were acquired from the anterior cingulate gyrus in nine healthy adults using 6.5-msec TE PR-STEAM, 40-msec TE PRESS, 72-msec TE STEAM, and TE-Averaging with an effective TE of 105 msec on a clinical 3T magnetic resonance imaging (MRI) system. All data were quantified using LCModel and reported as ratios relative to total creatine. RESULTS: Glutamate Cramer-Rao lower bounds were less than 8% for all sequences. The 6.5-msec TE PR-STEAM identified glutamate with the greatest precision (coefficient of variation [CV] of 7.1%), followed by TE-Averaging (CV of 8.9%), 40-msec TE PRESS (CV of 11.9%), and 72-msec TE STEAM (CV of 13.8%). CONCLUSION: In the absence of spectral editing, glutamate is best detected in the human brain at 3T using very short TEs.

Reconstructing very short TE phase rotation spectral data collected with multichannel phased-array coils at 3 T.

Phased-array volume coils were used in conjunction with the phase rotation STEAM (PR-STEAM) spectroscopy technique to acquire very short TE data from the anterior cingulate gyrus at 3 T. A method for combining PR-STEAM data from multiple subcoils is presented. The data were acquired from seven healthy participants using PR-STEAM (repetition time/mixing time/echo time=3500/10/6.5 ms, 6 cm(3), NEX=128, spectral width=2000 Hz, 2048 complex points, Δφ(1)=135°, Δφ(2)=22.5°, Δφ(3)=112.5° and Δφ(ADC)=0°). In addition to the primary metabolites, LCModel fit results suggest that glutathione and glutamate can also be identified with Cramér-Rao lower bounds of 10% or less.

Increased glucose concentration in the hippocampus in early Alzheimer's disease following oral glucose ingestion.

Glucose is the primary source of energy for brain cells. Because energy storage in the brain is limited, an uninterrupted supply of glucose and its rapid metabolism are essential for normal cognitive function. This study utilized an oral glucose load to examine hippocampal glucose metabolism in early Alzheimer's disease (AD) - a disease characterized by progressive deterioration of cognitive function and glucose hypometabolism. Short echo time 1H MR spectra (20 ms) from the right hippocampus of 8 patients with probable AD, 14 healthy elderly and 14 healthy young adults were compared pre- and post-glucose loading. In contrast to the healthy adults, the AD patients exhibited significantly elevated hippocampal glucose concentrations post-glucose ingestion relative to baseline (P < .01). These results suggest that cerebral glucose hypometabolism in AD leads to an increased steady-state concentration of cerebral glucose. This research demonstrates the feasibility of studying cerebral glucose metabolism in AD with 1H MR spectroscopy.

q-Space analysis of lung morphometry in vivo with hyperpolarized 3He spectroscopy.

PURPOSE: To examine the utility of a (3)He spectroscopic q-space technique for detecting changes in lung morphometry in vivo. MATERIALS AND METHODS: A diffusion-weighted spectroscopy sequence was used to collect global diffusion data from healthy adults (N = 11), healthy children (N = 5), and chronic obstructive pulmonary disease (COPD) patients (N = 2) using 40 cc of hyperpolarized (3)He gas within a two second breathhold. Displacement probability profiles (DPP) were obtained by Fourier transformation of diffusion data with respect to q. A bi-Gaussian model was used to decompose the DPPs into narrow and broad components, characterized by root-mean-square displacements X(rms1) and X(rms2), respectively. RESULTS: In healthy adults, the narrow component (X(rms,1)) of the DPP had a mean displacement of 188 +/- 10 microm, slightly less than the reported average size of the alveoli. The broad component (X(rms,2)) had a mean value of 474 +/- 44 microm, comparable to the diameter of the respiratory bronchioles in the acinus. In children, both X(rms1) (167 +/- 4 microm) and X(rms2) (382 +/- 22 microm) compared to healthy adults (P < 0.01). In COPD patients, the mean displacements were elevated (X(rms1): 265 +/- 71 microm; X(rms2): 530 +/- 109 microm) compared to healthy adults. Excellent correlation was found between rms displacements and age (age vs. X(rms,1): r = 0.78, P < 0.001; age vs. X(rms,2): r = 0.90, P < 0.001). CONCLUSION: The q-space parameters agreed remarkably well with published alveolar morphometry data. The results suggest that the technique may be sensitive to disease, as evident from the elevated mean displacements in COPD patients compared to healthy volunteers. Detailed lung microstructural information can be obtained using a very low volume of inhaled (3)He.

A phase rotation scheme for achieving very short echo times with localized stimulated echo spectroscopy.

In a single-voxel stimulated echo localization sequence in magnetic resonance spectroscopy, magnetic field gradients are inserted within the echo time (TE) to filter signals generated through coherence pathways other than that leading to the stimulated echo. There is a significant penalty for these gradients as they increase the minimum TE, thereby leading to significant signal loss from spin-spin relaxation and phase distortions in coupled spin systems. Here, an RF phase rotation technique is described for a stimulated echo localization sequence that allows removal of the gradients in the TE intervals and, subsequently, reduction of the minimum TE to only 6 ms. Experiments carried out on six healthy volunteers on a 1.5-T whole-body MR system show a significant signal increase in the metabolite concentrations when measured with a 6-ms TE (N-acetyl-aspartate, 12%, P=.002; creatine, 15%, P=.04; and glutamate+glutamine, 92%, P=.02) compared to concentrations measured with data collected at TEs of 15 and 20 ms.

Increasing the speed of relaxometry-based compartmental analysis experiments in STEAM spectroscopy.

In this work we present a method for improving the speed of spin-spin relaxation time (T2) measurements for compartmental analysis in stimulated echo localized magnetic resonance spectroscopy without reducing the sampling density. The technique uses a progressive repetition time (TR) to compensate for echo time (TE) dependent variations in saturation effects that would otherwise modulate the received signal at short TRs. The method was validated in T2 studies on 10 young healthy subjects in spectroscopic voxels localized along either the right or left Sylvian fissure (2 x 2 x 1.5 cm3, 10 ms mixing time (TM), 2048 data points, 819.2 ms acquisition time). The TR was automatically adjusted so that TR-TM-TE/2 was kept constant as the TE was incremented. Compared to long TR T2 experiments, the progressive TR technique consistently replicated the T2 relaxation times and reference signals of the tissue water compartment while reducing the data acquisition time by more than 50%. The percent error was on average less than 2% for estimates of T2 and S(0) for the tissue water, an indication that the progressive TR technique is a useful method for determining the tissue water signal for internal referencing.

Shortening of hippocampal spin-spin relaxation time in probable Alzheimer's disease: a 1H magnetic resonance spectroscopy study.

We quantified the differential effects of the spin-spin relaxation times (T2) of tissue water and cerebral spinal fluid in order to examine hippocampal T2 changes as a non-invasive bio-marker of Alzheimer's disease (AD). We measured T2 in the right hippocampus of ten patients fulfilling the NINCDS-ADRDA criteria for AD and 40 healthy adult volunteers using localized proton magnetic resonance spectroscopy. The T2 values of AD patients (73 +/- 8 ms) were significantly shorter (P < 0.01) than those of healthy age-matched controls (81 +/- 5 ms), and there was a reduction in T2 for healthy older vs. healthy younger adults (87 +/- 5 ms, P < 0.05). The reduced T2 values with aging are consistent with age-related decreases in tissue water content. Our results suggest that there may be a severe reduction in tissue water content in AD.

Molality as a unit of measure for expressing 1H MRS brain metabolite concentrations in vivo.

Absolute concentrations of cerebral metabolite in in vivo 1H magnetic resonance spectroscopy studies (1H-MRS) are widely reported in molar units as moles per liter of tissue, or in molal units as moles per kilogram of tissue. Such measurements require external referencing or assumptions as to local water content. To reduce the scan time, avoid assumptions that may be invalid under specific pathologies, and provide a universally accessible referencing procedure, we suggest that metabolite concentrations from 1H-MRS measurements in vivo be reported in molal units as moles per kilogram of tissue water. Using internal water referencing, a two-compartment water model, a simulated brain spectrum for peak identification, and a spectroscopic bi-exponential spin-spin relaxation segmentation technique, we measured the absolute concentrations for the four common 1H brain metabolites: choline (Cho), myo-inositol (mIno), phosphocreatine + creatine (Cr), and N-acetyl-aspartate (NAA), in the hippocampal region (n = 26) and along the Sylvian fissure (n = 61) of 35 healthy adults. A stimulated echo localization method (20 ms echo time, 10 ms mixing time, 4 s repetition time) yielded metabolite concentrations, uncorrected for metabolite relaxation or contributions from macromolecule resonances, that were expectantly higher than with molar literature values. Along the Sylvian fissure the average concentrations (coefficient of variation (CV)) in mmoles/kg of tissue water were 17.6 (12%) for NAA, 14.2 (9%) for Cr, 3.6 (13%) for Cho, and 13.2 (15%) for mIno. Respective values for the hippocampal region were 15.7 (20%), 14.7 (16%), 4.6 (19%), and 17.7 (26%). The concentrations of the two regions were significantly different (p

Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: assessment of response to methacholine and exercise challenge.

BACKGROUND: Imaging of gas distribution in the lungs of patients with asthma has been restricted because of the lack of a suitable gaseous contrast agent. Hyperpolarized helium-3 (HHe3) provides a new technique for magnetic resonance imaging of lung diseases. OBJECTIVE: We sought to investigate the use of HHe3 gas to image the lungs of patients with moderate or severe asthma and to assess changes in gas distribution after methacholine and exercise challenge. METHODS: Magnetic resonance imaging was performed in asthmatic patients immediately after inhalation of HHe3 gas. In addition, images were obtained before and after methacholine challenge and a standard exercise test. RESULTS: Areas of the lung with no signal or sharply reduced HHe3 signal (ventilation defects) are common in patients with asthma, and the number of defects was inversely related to the percent predicted FEV(1) (r = 0.71, P <.002). After methacholine challenge (n = 3), the number of defects increased. Similarly, imaging of the lungs after exercise (n = 6) showed increased ventilation defects in parallel with decreases in FEV(1). The increase in defects after challenge in these 9 asthmatic patients was significant both for the number (P <.02) and extent (P <.02) of the defects. The variability and speed of changes in ventilation and the complete lack of signal in many areas is in keeping with a model in which the defects result from airway closure. CONCLUSION: HHe3 magnetic resonance provides a new technique for imaging the distribution of inhaled air in the lungs. The technique is suitable for following responses to treatment of asthma and changes after methacholine or exercise challenge.

Constrained modeling for spectroscopic measurement of bi-exponential spin-lattice relaxation of water in vivo.

The (1)H NMR water signal from spectroscopic voxels localized in gray matter contains contributions from tissue and cerebral spinal fluid (CSF). A typically weak CSF signal at short echo times makes separating the tissue and CSF spin-lattice relaxation times (T(1)) difficult, often yielding poor precision in a bi-exponential relaxation model. Simulations show that reducing the variables in the T(1) model by using known signal intensity values significantly improves the precision of the T(1) measurement. The method was validated on studies on eight healthy subjects (four males and four females, mean age 21 +/- 2 years) through a total of twenty-four spectroscopic relaxation studies. Each study included both T(1) and spin-spin relaxation (T(2)) experiments. All volumes were localized along the Sylvian fissure using a stimulated echo localization technique with a mixing time of 10 ms. The T(2) experiment consisted of 16 stimulated echo acquisitions ranging from a minimum echo time (TE) of 20 ms to a maximum of 1000 ms, with a repetition time of 12 s. All T(1) experiments consisted of 16 stimulated echo acquisition, using a homospoil saturation recovery technique with a minimum recovery time of 50 ms and a maximum 12 s. The results of the T(2) measurements provided the signal intensity values used in the bi-exponential T(1) model. The mean T(1) values when the signal intensities were constrained by the T(2) results were 1055.4 ms +/- 7.4% for tissue and 5393.5 ms +/- 59% for CSF. When the signal intensities remained free variables in the model, the mean T(1) values were 1085 ms +/- 19.4% and 5038.8 ms +/- 113.0% for tissue and CSF, respectively. The resulting improvement in precision allows the water tissue T(1) value to be included in the spectroscopic characterization of brain tissue.

Ventilation-perfusion ratio of signal intensity in human lung using oxygen-enhanced and arterial spin labeling techniques.

This study investigates the distribution of ventilation-perfusion (V/Q) signal intensity (SI) ratios using oxygen-enhanced and arterial spin labeling (ASL) techniques in the lungs of 10 healthy volunteers. Ventilation and perfusion images were simultaneously acquired using the flow-sensitive alternating inversion recovery (FAIR) method as volunteers alternately inhaled room air and 100% oxygen. Images of the T(1) distribution were calculated for five volunteers for both selective (T(1f)) and nonselective (T(1)) inversion. The average T(1) was 1360 ms +/- 116 ms, and the average T(1f) was 1012 ms +/- 112 ms, yielding a difference that is statistically significant (P < 0.002). Excluding large pulmonary vessels, the average V/Q SI ratios were 0.355 +/- 0.073 for the left lung and 0.371 +/- 0.093 for the right lung, which are in agreement with the theoretical V/Q SI ratio. Plots of the V/Q SI ratio are similar to the logarithmic normal distribution obtained by multiple inert gas elimination techniques, with a range of ratios matching ventilation and perfusion. This MRI V/Q technique is completely noninvasive and does not involve ionized radiation. A limitation of this method is the nonsimultaneous acquisition of perfusion and ventilation data, with oxygen administered only for the ventilation data.