Utilization of 19F MRI for Identification of Iraq-Afghanistan War Lung Injury.

INTRODUCTION: There is mounting evidence of respiratory problems related to military service in the Middle East in the past two decades due to environmental exposures during deployment (eg, sand storms and burn pits). This pilot study tests the hypothesis that regional lung function in subjects with prior deployment in Iraq and/or Afghanistan with suspected War Lung Injury (WLI) would be worse than subjects with normal lung function. MATERIALS AND METHODS: Five subjects meeting the inclusion and exclusion criteria were recruited for this pilot study. All subjects underwent spirometry, high-resolution chest computed tomography imaging, and 19F MRI. RESULTS: While the WLI subjects had normal pulmonary function tests and normal high-resolution chest computed tomography evaluations, their regional lung function from 19F MRI was abnormal with compartments with poor function showing slower filling time constants for ventilation. The scans of suspected WLI subjects show higher fractional lung volume with slow filling compartments similar to patients with chronic obstructive pulmonary disease in contrast to normal subjects. CONCLUSIONS: This is consistent with our premise that WLI results in abnormal lung function and reflects small airways dysfunction and suggests that we may be able to provide a more sensitive tool for evaluation of WLI suspected cases.

Dynamic perfluorinated gas MRI reveals abnormal ventilation despite normal FEV1 in cystic fibrosis.

We hypothesized that dynamic perfluorinated gas MRI would sensitively detect mild cystic fibrosis (CF) lung disease. This cross-sectional study enrolled 20 healthy volunteers and 24 stable subjects with CF, including a subgroup of subjects with normal forced expiratory volume in the first second (FEV1; >80% predicted, n = 9). Dynamic fluorine-19-enhanced MRI (19F MRI) were acquired during sequential breath holds while breathing perfluoropropane (PFP) and during gas wash-out. Outcomes included the fraction of lung without significant ventilation (ventilation defect percent, VDP) and time constants that described PFP wash-in and wash-out kinetics. VDP values (mean ± SD) of healthy controls (3.87% ± 2.7%) were statistically different from moderate CF subjects (19.5% ± 15.5%, P = 0.001) but not from mild CF subjects (10.4% ± 9.9%, P = 0.24). In contrast, the fractional lung volume with slow gas wash-out was elevated both in subjects with mild (9.61% ± 4.87%; P = 0.0066) and moderate CF (16.01% ± 5.01%; P = 0.0002) when compared with healthy controls (3.84% ± 2.16%) and distinguished mild from moderate CF (P = 0.006). 19F MRI detected significant ventilation abnormalities in subjects with CF. The ability of gas wash-out kinetics to distinguish between healthy and mild CF lung disease subjects makes 19F MRI a potentially valuable method for the characterization of early lung disease in CF. This study has been registered at ClinicalTrials.gov (NCT03489590).

Pulmonary Delivery of Therapeutic and Diagnostic Gases.

The 21st Congress for the International Society for Aerosols in Medicine included, for the first time, a session on Pulmonary Delivery of Therapeutic and Diagnostic Gases. The rationale for such a session within ISAM is that the pulmonary delivery of gaseous drugs in many cases targets the same therapeutic areas as aerosol drug delivery, and is in many scientific and technical aspects similar to aerosol drug delivery. This article serves as a report on the recent ISAM congress session providing a synopsis of each of the presentations. The topics covered are the conception, testing, and development of the use of nitric oxide to treat pulmonary hypertension; the use of realistic adult nasal replicas to evaluate the performance of pulsed oxygen delivery devices; an overview of several diagnostic gas modalities; and the use of inhaled oxygen as a proton magnetic resonance imaging (MRI) contrast agent for imaging temporal changes in the distribution of specific ventilation during recovery from bronchoconstriction. Themes common to these diverse applications of inhaled gases in medicine are discussed, along with future perspectives on development of therapeutic and diagnostic gases.

Predictive Validity of Radiographic Trabecular Bone Texture in Knee Osteoarthritis: The Osteoarthritis Research Society International/Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.

OBJECTIVE: To evaluate radiographic subchondral trabecular bone texture (TBT) as a predictor of clinically relevant osteoarthritis (OA) progression (combination of symptom and structural worsening). METHODS: The Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium undertook a study of progressive knee OA cases (n = 194 knees with both radiographic and pain progression over 24-48 months) and comparators (n = 406 OA knees not meeting the case definition). TBT parameters were extracted from a medial subchondral tibial region of interest by fractal signature analysis of radiographs using validated semiautomated software. Baseline TBT and time-integrated values over 12 and 24 months were evaluated for association with case status and separately with radiographic and pain progression status, adjusted for age, sex, body mass index, race, baseline Kellgren/Lawrence grade, baseline joint space width, Western Ontario and McMaster Universities Osteoarthritis Index pain score, and pain medication use. C statistics were generated from receiver operating characteristic curves. RESULTS: Relative to comparators, cases were characterized by thinner vertical and thicker horizontal trabeculae. The summed composite of 3 TBT parameters at baseline and over 12 and 24 months best predicted case status (odds ratios 1.24-1.43). The C statistic for predicting case status using the TBT composite score (0.633-0.649) was improved modestly but statistically significantly over the use of covariates alone (0.608). One TBT parameter, reflecting thickened horizontal trabeculae in cases, at baseline and over 12 and 24 months, predicted risk of any progression (radiographic and/or pain progression). CONCLUSION: Although associations are modest, TBT could be an attractive means of enriching OA trials for progressors since it can be generated from screening knee radiographs already standard in knee OA clinical trials.

Diseased Region Detection of Longitudinal Knee Magnetic Resonance Imaging Data.

Magnetic resonance imaging (MRI) has become an important imaging technique for quantifying the spatial location and magnitude/direction of longitudinal cartilage morphology changes in patients with osteoarthritis (OA). Although several analytical methods, such as subregion-based analysis, have been developed to refine and improve quantitative cartilage analyses, they can be suboptimal due to two major issues: the lack of spatial correspondence across subjects and time and the spatial heterogeneity of cartilage progression across subjects. The aim of this paper is to present a statistical method for longitudinal cartilage quantification in OA patients, while addressing these two issues. The 3D knee image data is preprocessed to establish spatial correspondence across subjects and/or time. Then, a Gaussian hidden Markov model (GHMM) is proposed to deal with the spatial heterogeneity of cartilage progression across both time and OA subjects. To estimate unknown parameters in GHMM, we employ a pseudo-likelihood function and optimize it by using an expectation-maximization (EM) algorithm. The proposed model can effectively detect diseased regions in each OA subject and present a localized analysis of longitudinal cartilage thickness within each latent subpopulation. Our GHMM integrates the strengths of two standard statistical methods including the local subregion-based analysis and the ordered value approach. We use simulation studies and the Pfizer longitudinal knee MRI dataset to evaluate the finite sample performance of GHMM in the quantification of longitudinal cartilage morphology changes. Our results indicate that GHMM significantly outperforms several standard analytical methods.

Physiorack: an integrated MRI safe/conditional, gas delivery, respiratory gating, and subject monitoring solution for structural and functional assessments of pulmonary function.

PURPOSE: To evaluate the use of a modular MRI conditional respiratory monitoring and gating solution, designed to facilitate proper monitoring of subjects' vital signals and their respiratory efforts, during free-breathing and breathheld 19F, oxygen-enhanced, and Fourier-decomposition MRI-based acquisitions. MATERIALS AND METHODS: All Imaging was performed on a Siemens TIM Trio 3 Tesla MRI scanner, following Institutional Review Board approval. Gas delivery is accomplished through the use of an MR compatible pneumotachometer, in conjunction with two three-way pneumatically controlled Hans Rudolph Valves. The pneumatic valves are connected to Douglas bags used as the gas source. A mouthpiece (+nose clip) or an oro-nasal Hans Rudolph disposable mask is connected following the pneumatic valve to minimize dead-space and provide an airtight seal. Continuous monitoring/sampling of inspiratory and expiratory oxygen and carbon dioxide levels at the mouthpiece/mask is achieved through the use of an Oxigraf gas analyzer. RESULTS: Forty-four imaging sessions were successfully monitored, during Fourier-decomposition (n=3), fluorine-enhanced (n=29), oxygen-enhanced, and ultra short echo (n=12) acquisitions. The collected waveforms, facilitated proper monitoring and coaching of the subjects. CONCLUSION: We demonstrate an inexpensive, off-the-shelf solution for monitoring these signals, facilitating assessments of lung function. Monitoring of respiratory efforts and exhaled gas concentrations assists in understanding the heterogeneity of lung function visualized by gas imaging.

Perfluoropropane gas as a magnetic resonance lung imaging contrast agent in humans.

BACKGROUND: Fluorine-enhanced MRI is a relatively inexpensive and straightforward technique that facilitates regional assessments of pulmonary ventilation. In this report, we assess its suitability through the use of perfluoropropane (PFP) in a cohort of human subjects with normal lungs and subjects with lung disease. METHODS: Twenty-eight subjects between the ages of 18 and 71 years were recruited for imaging and were classified based on spirometry findings and medical history. Imaging was carried out on a Siemens TIM Trio 3T MRI scanner using two-dimensional, gradient echo, fast low-angle shot and three-dimensional gradient echo, volumetric, interpolated, breath-hold examination sequences for proton localizers and PFP functional scans, respectively. Respiratory waveforms and physiologic signals of interest were monitored throughout the imaging sessions. A region-growing algorithm was applied to the proton localizers to define the lung field of view for analysis of the PFP scans. RESULTS: All subjects tolerated the gas mixture well with no adverse side effects. Images of healthy lungs demonstrated a homogeneous distribution of the gas with sufficient signal-to-noise ratios, while lung images from asthmatic and emphysematous lungs demonstrated increased heterogeneity and ventilation defects. CONCLUSIONS: Fluorine-enhanced MRI using a normoxic PFP gas mixture is a well-tolerated, radiation-free technique for regionally assessing pulmonary ventilation. The inherent physical characteristics and applicability of the gaseous agent within a magnetic resonance setting facilitated a clear differentiation between normal and diseased lungs.

Subchondral bone trabecular integrity predicts and changes concurrently with radiographic and magnetic resonance imaging-determined knee osteoarthritis progression.

OBJECTIVE: To evaluate subchondral bone trabecular integrity (BTI) on radiographs as a predictor of knee osteoarthritis (OA) progression. METHODS: Longitudinal (baseline, 12-month, and 24-month) knee radiographs were available for 60 female subjects with knee OA. OA progression was defined by 12- and 24-month changes in radiographic medial compartment minimal joint space width (JSW) and medial joint space area (JSA), and by medial tibial and femoral cartilage volume on magnetic resonance imaging. BTI of the medial tibial plateau was analyzed by fractal signature analysis using commercially available software. Receiver operating characteristic (ROC) curves for BTI were used to predict a 5% change in OA progression parameters. RESULTS: Individual terms (linear and quadratic) of baseline BTI of vertical trabeculae predicted knee OA progression based on 12- and 24-month changes in JSA (P < 0.01 for 24 months), 24-month change in tibial (P < 0.05), but not femoral, cartilage volume, and 24-month change in JSW (P = 0.05). ROC curves using both terms of baseline BTI predicted a 5% change in the following OA progression parameters over 24 months with high accuracy, as reflected by the area under the curve measures: JSW 81%, JSA 85%, tibial cartilage volume 75%, and femoral cartilage volume 85%. Change in BTI was also significantly associated (P < 0.05) with concurrent change in JSA over 12 and 24 months and with change in tibial cartilage volume over 24 months. CONCLUSION: BTI predicts structural OA progression as determined by radiographic and MRI outcomes. BTI may therefore be worthy of study as an outcome measure for OA studies and clinical trials.

Trabecular morphometry by fractal signature analysis is a novel marker of osteoarthritis progression.

OBJECTIVE: To evaluate the effectiveness of using subchondral bone texture observed on a radiograph taken at baseline to predict progression of knee osteoarthritis (OA) over a 3-year period. METHODS: A total of 138 participants in the Prediction of Osteoarthritis Progression study were evaluated at baseline and after 3 years. Fractal signature analysis (FSA) of the medial subchondral tibial plateau was performed on fixed flexion radiographs of 248 nonreplaced knees, using a commercially available software tool. OA progression was defined as a change in joint space narrowing (JSN) or osteophyte formation of 1 grade according to a standardized knee atlas. Statistical analysis of fractal signatures was performed using a new model based on correlating the overall shape of a fractal dimension curve with radius. RESULTS: Fractal signature of the medial tibial plateau at baseline was predictive of medial knee JSN progression (area under the curve [AUC] 0.75, of a receiver operating characteristic curve) but was not predictive of osteophyte formation or progression of JSN in the lateral compartment. Traditional covariates (age, sex, body mass index, knee pain), general bone mineral content, and joint space width at baseline were no more effective than random variables for predicting OA progression (AUC 0.52-0.58). The predictive model with maximum effectiveness combined fractal signature at baseline, knee alignment, traditional covariates, and bone mineral content (AUC 0.79). CONCLUSION: We identified a prognostic marker of OA that is readily extracted from a plain radiograph using FSA. Although the method needs to be validated in a second cohort, our results indicate that the global shape approach to analyzing these data is a potentially efficient means of identifying individuals at risk of knee OA progression.

Hyperthermia MRI temperature measurement: evaluation of measurement stabilisation strategies for extremity and breast tumours.

PURPOSE: MR thermometry using the proton resonance frequency shift (PRFS) method has been used to measure temperature changes during clinical hyperthermia treatment. However, frequency drift of the MRI system can add large errors to the measured temperature change. These drifts can be measured and corrected using oil references placed around the treatment region. In this study, the number and position of four or more oil references were investigated to obtain a practical approach to correct frequency drift during PRFS thermometry in phantoms and in vivo. MATERIALS AND METHODS: Experiments were performed in a 140 MHz four antenna mini-annular phased array (MAPA) heat applicator (for treatment of extremity tumours) and an applicator for heating of the breast, with symmetric and asymmetric positioning of the oil references, respectively. Temperature change PRFS images were obtained during an hour or more of measurement with no application of heat. Afterwards, errors in calculating temperature change due to system drift were quantified with and without various oil reference correction arrangements. RESULTS: Results showed good temperature correction in phantoms and in a human leg, with average errors of 0.28 degrees C and 0.94 degrees C respectively. There was further improvement in the leg when using eight or more oil references, reducing the average error to 0.44 degrees C, while the phantoms showed no significant improvement. CONCLUSIONS: These results indicate that oil reference correction performs well in vivo, and that eight references can improve the correction by up to 0.5 degrees C compared to four references.

Quantitative imaging of cartilage morphology at 3.0 Tesla in the presence of gadopentate dimeglumine (Gd-DTPA).

MRI-based cartilage morphometry was previously validated in the absence of gadopentate dimeglumine (Gd-DTPA). However, Gd-DTPA is required for compositional (proteoglycan) imaging using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Therefore, the effect of Gd-DTPA on cartilage morphometry was studied. A total of 165 female participants (67 with and 98 without osteoarthritis [OA]) were imaged at 3.0 Tesla before and 2 hr after intravenous Gd-DTPA injection. Flip angles in post-Gd-DTPA scans varied between 12 degrees and 35 degrees . Cartilage volume and thickness of post- vs. pre-Gd-DTPA scans showed intraclass correlation coefficients (ICCs) of 0.85 > or = r > or = 0.95, mean differences between -2.1% and +1.1%, and standard deviations (SDs) of differences between 4.7% and 9.2%. Mixed-effect models found no consistent impact of flip angle and OA status on post- vs. pre-Gd-DTPA differences. Accurate morphological measurements of cartilage can be obtained after Gd-DTPA injection, allowing compositional and morphological imaging to be combined into one session.

Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the InDDEx study.

OBJECTIVE: To assess the effect of rivastigmine in patients with mild cognitive impairment (MCI) on the time to clinical diagnosis of Alzheimer's disease (AD) and the rate of cognitive decline. METHODS: The study was a double-blind, randomised, placebo-controlled trial of up to 48 months. All patients had MCI operationally defined by having cognitive symptoms, a global clinical dementia rating stage of 0.5, a score of less than 9 on the New York University delayed paragraph recall test, and by not meeting the diagnostic criteria for AD. Primary efficacy variables were time to clinical diagnosis of AD, and change in performance on a cognitive test battery. This study is registered with the US National Institutes of Health clinical trials database (ClinicalTrials.gov), number NCT00000174. FINDINGS: Of 1018 study patients enrolled, 508 were randomly assigned to rivastigmine and 510 to placebo; 17.3% of patients on rivastigmine and 21.4% on placebo progressed to AD (hazard ratio 0.85 [95% CI 0.64-1.12]; p=0.225). There was no significant difference between the rivastigmine and placebo groups on the standardised Z score for the cognitive test battery measured as mean change from baseline to endpoint (-0.10 [95% CI -0.63 to 0.44], p=0.726). Serious adverse events were reported by 141 (27.9%) rivastigmine-treated patients and 155 (30.5%) patients on placebo; adverse events of all types were reported by 483 (95.6%) rivastigmine-treated patients and 472 (92.7%) placebo-treated patients. The predominant adverse events were cholinergic: the frequencies of nausea, vomiting, diarrhoea, and dizziness were two to four times higher in the rivastigmine group than in the placebo group. INTERPRETATION: There was no significant benefit of rivastigmine on the progression rate to AD or on cognitive function over 4 years. The overall rate of progression from MCI to AD in this randomised clinical trial was much lower than predicted. Rivastigmine treatment was not associated with any significant safety concerns.

Predicting memory decline in normal elderly: genetics, MRI, and cognitive reserve.

Major predictors of Alzheimer's disease (AD) include apolipoprotein E (APOE)-epsilon4, hippocampal atrophy on magnetic resonance imaging (MRI), and memory dysfunction prior to diagnosis. We examined 159 normal elderly subjects with MRI and the California Verbal Learning Test (CVLT); 84 returned for longitudinal follow-up 5 years later. Analyses at baseline revealed significant variance in hippocampal volume accounted for by cerebral volume and age but not by APOE isoform. However, interactions involving APOE isoform and laterality were observed. As hypothesized, an APOE x time interaction was revealed for CVLT long-delay free recall: APOE-epsilon3/4 subjects had significantly poorer performance than APOE-epsilon3/3 subjects at follow-up. Forward stepwise multiple regression analysis predicting follow-up long-delay free recall selected baseline recall, followed by number of APOE-epsilon4 alleles, followed by left-hippocampal volume. Age and sex did not enter into the model. We conclude that APOE-epsilon4 predicts longitudinal memory decline in healthy controls and that MRI morphometry of hippocampus adds slightly to predictive value.

Extracellular pH and P-31 magnetic resonance spectroscopic variables are related to outcome in canine soft tissue sarcomas treated with thermoradiotherapy.

PURPOSE: The objective was to test whether tumor pH and (31)P magnetic resonance spectroscopic end points were related to treatment outcome in pet canine patients with spontaneous soft tissue sarcomas treated with thermoradiotherapy. EXPERIMENTAL DESIGN: Forty-two dogs with evaluable (31)P magnetic resonance spectroscopic end points and pH data were included in this study. Tumor variables (grade and volume), extracellular pH (pHe), T(2) relaxation times, intracellular pH, and selected phosphometabolite ratios were examined for correlation with clinical outcome. RESULTS: From 39 dogs, pHe was a predictor of metastasis-free survival (MFS), with hazard ratio (HR, 0.29; P = 0.005) and overall survival (OS) with (HR, 0.36; P = 0.013). Tumor volume (>19 cm(3)) was related to MFS (HR, 2.14; P = 0.04), time to local failure (HR, 3.4; P = 0.025), and OS (HR, 2.27; P = 0.03). There was no association between T(2) or intracellular pH and clinical outcome. Tumor grade (high versus low/intermediate) and phosphodiester/betaATP ratio were identified as significant predictors for MFS, with (HR, 2.66; P = 0.009) and (HR, 0.75; P = 0.027), respectively, and as predictors of OS with (HR, 2.66; P = 0.009) and (HR, 0.76; P = 0.03), respectively. The phosphodiester/phosphocreatinine ratio predicted time to local failure (HR, 1.24; P = 0.017). CONCLUSIONS: pHe was predictive of metastasis and OS in canine spontaneous sarcomas. To our knowledge, this is the first time that pHe has been shown to be predictive of clinical outcome. The results suggest that additional studies should be considered evaluating the prognostic significance of this variable. Phospholipid resonances, related to membrane metabolism, were related to clinical outcome, confirming recent results reported in human patients with soft tissue sarcomas treated with thermoradiotherapy.

Accuracy and precision of quantitative assessment of cartilage morphology by magnetic resonance imaging at 3.0T.

OBJECTIVE: Quantitative magnetic resonance imaging (MRI) of articular cartilage represents a powerful tool in osteoarthritis (OA) research, but has so far been confined to a field strength of 1.5T. The aim of this study was to evaluate the precision of quantitative MRI assessments of human cartilage morphology at 3.0T and to correlate the measurements at 3.0T with validated measurements at 1.5T. METHODS: MR images of the knee of 15 participants with OA and 15 healthy control subjects were acquired using Siemens 1.5T and 3.0T scanners. Double oblique coronal scans were obtained at 1.5T with a 1.5-mm partition thickness, at 3.0T with a 1.5-mm partition thickness, and at 3.0T with a 1.0-mm partition thickness. Cartilage volume, thickness, and surface area of the femorotibial cartilage plates were quantified using proprietary software. RESULTS: For 1.5-mm partition thickness at 1.5T, the precision error was 3.0% and 2.6% for cartilage volume and cartilage thickness, respectively. The error was smaller for a 1.5-mm partition thickness at 3.0T (2.6% and 2.5%) and still smaller for a 1.0-mm partition thickness at 3.0T (2.1% and 2.0%). Correlation coefficients between values obtained at 3.0T and 1.5T were high (r > or = 0.96), with no significant deviation between the two field strengths. CONCLUSION: Quantitative MRI measurement of cartilage morphology at 3.0T (partition thickness 1 mm) was found to be accurate and tended to be more reproducible than at 1.5T (partition thickness 1.5 mm). Imaging at 3.0T may therefore provide superior ability to detect changes in cartilage status over time and to determine responses to treatment with structure-modifying drugs.

Relation between pO2, 31P magnetic resonance spectroscopy parameters and treatment outcome in patients with high-grade soft tissue sarcomas treated with thermoradiotherapy.

PURPOSE: In a prior study, the combination of (31)P magnetic resonance spectroscopy (MRS)-based intracellular pH (pHi) and T2 relaxation time was highly predictive of the pathologic complete response (pCR) rate in a small series of patients with soft tissue sarcomas (STSs) treated with thermoradiotherapy. Changes in the magnetic resonance metabolite ratios and pO(2) were related to the pCR rate. Hypoxia also correlated with a greater likelihood for the development of metastases. Because of the limited number of patients in the prior series, we initiated this study to determine whether the prior observations were repeatable and whether (31)P MRS lipid-related resonances were related to a propensity for metastasis. METHODS AND MATERIALS: Patients with high-grade STSs were enrolled in an institutional review board-approved Phase II thermoradiotherapy trial. All tumors received daily external beam radiotherapy (1.8-2.0 Gy, five times weekly) to a total dose of 30-50 Gy. Hyperthermia followed radiotherapy by <1 h and was given two times weekly. Tumors were resected 4-6 weeks after radiotherapy completion. The MRS/MRI parameters included (31)P metabolite ratios, pHi, and T2 relaxation time. The median pO(2) and hypoxic fraction were determined using pO(2) histography. Comparisons between experimental endpoints and the pCR rate and metastasis-free and overall survival were made. RESULTS: Of 35 patients, 21 and 28 had reportable pretreatment MRS/MRI and pO(2) data, respectively. The cutpoints for a previously tested receiver operating curve for a pCR were T2 = 100 and pHi = 7.3. In the current series, few tumors fell below the cutpoints so validation was not possible. The phosphodiester (PDE)/inorganic phosphate (Pi) ratio and hypoxic fraction correlated inversely with the pCR rate in the current series (Spearman correlation coefficient -0.51, p = 0.017; odds ratio of percentage of necrosis > or =95% = 0.01 for a 1% increase in the hypoxic fraction; Wald p = 0.036). The pretreatment phosphomonoester (PME)/Pi ratio also correlated inversely with the pCR rate (odds ratio of percentage of necrosis > or =95% = 0.06 for pretreatment PME/Pi ratio >0.8 vs. < or =0.8, Wald p = 0.023). The pretreatment PME/PDE ratio correlated strongly with metastasis-free survival and overall survival (p = 0.012 and hazard ratio = 5.8, and p = 0.038 and hazard ratio = 6.75, respectively). CONCLUSION: The dual parameter model containing pHi and T2 to predict the pCR in STSs treated with thermoradiotherapy was not verified. However, other parameters were statistically significant, including the PDE/Pi ratio and hypoxic fraction. These relationships may have interfered with our ability to obtain the pCR rate predicted by thermal doses achieved in these patients. The relationship between the PME/PDE ratio and metastasis-free and overall survival was provocative, but requires additional study to verify its predictive capability. Currently, 50% of all STS patients with high-grade tumors develop distant metastasis even when excellent local control is achieved. Parameters that could help select for patients who need adjuvant chemotherapy could have significant clinical benefit.

A review of 1H MR spectroscopy findings in Alzheimer's disease.

Hydrogen-1 MR spectroscopy (MRS) studies demonstrate metabolic differences between patients who have Alzheimer's disease (AD) and cognitive normal age-matched controls. Clinical MRS also shows regional variations in metabolites between patients who have AD and those who have other dementias. Single-voxel and volumetric standard MRS techniques and automated data processing software are available for clinical MR scanners. Improvements in specificity and sensitivity of AD diagnosis, using MRS techniques as an adjunct to clinical imaging, are under evaluation. Multiparametric data analyses show, however, that metabolite changes correlate with in-vitro, postmortem, and metabolic changes and to changes in or predictions of cognitive scores.

Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer's disease.

OBJECTIVE: The authors examined the effect of the acetylcholinesterase inhibitor donepezil on magnetic resonance markers of neurodegeneration in Alzheimer's disease. METHOD: In this randomized, double-blind, placebo-controlled pilot study, 67 patients with mild to moderate Alzheimer's disease received 24 weeks of treatment with donepezil (5 mg/day for the first 28 days and 10 mg/day thereafter) or placebo. Patients were reevaluated at 6-week intervals to measure change from baseline in several outcome measures, including right, left, and total hippocampal volumes, measured with magnetic resonance imaging; brain concentrations of N-acetylaspartate, measured with proton magnetic resonance spectroscopy; and cognition, assessed with the Alzheimer's Disease Assessment Scale cognitive subscale. RESULTS: At some interim assessments, mean normalized measures of N-acetylaspartate concentration tended to be higher in the donepezil-treated patients than in the patients who received placebo, but these differences were not significant at endpoint. At endpoint, the donepezil-treated patients had significantly smaller mean decreases in total and right hippocampal volumes and a smaller, nearly significant mean decrease in left hippocampal volume, compared with the placebo-treated patients. Mean Alzheimer's Disease Assessment Scale cognitive subscale scores were improved after treatment with donepezil, relative to placebo, at weeks 6, 12, 18, and 24. CONCLUSIONS: These preliminary results suggest that donepezil may have a potentially protective effect in Alzheimer's disease. Larger, longer-term confirmatory studies of the medication's effects are warranted.

Focal and lateralized subcortical abnormalities in unipolar major depressive disorder: an automated multivoxel proton magnetic resonance spectroscopy study.

BACKGROUND: The results of prior proton magnetic resonance spectroscopy ((1)H-MRS) studies in unipolar major depressive disorder (MDD) evaluating choline (Cho)/creatine (Cr) and N-acetyl-L-aspartate (NAA)/Cr ratios are mixed. These single-voxel or one-dimensional chemical-shift imaging (CSI) nonautomated (1)H-MRS studies has been unable to evaluate global or lateralized abnormalities in neuronal or membrane function. Using automated multivoxel two-dimensional CSI (1)H-MRS techniques, we tested the hypothesis that patients with MDD have focal neuronal and membrane abnormalities localized in the subcortical region. METHODS: Whole brain and subcortical measures of Cho, NAA, Cr, and myo-inositol (mI) were obtained in 18 patients with MDD and 20 control subjects using automated two-dimensional CSI (1)H-MRS. RESULTS: Compared with control subjects, MDD patients had a significantly lower mean NAA/Cr amplitude in the caudate and a significantly higher mean Cho/Cr amplitude in the putamen, particularly on the right side. No differences were observed for global whole brain measurements. CONCLUSIONS: The findings support reduced neuronal viability or function in the caudate and altered membrane phospholipid metabolism in the putamen for patients with MDD. Our results are consistent with prior magnetic resonance imaging, positron emission tomography, and postmortem reports of focal and lateralized abnormalities of the basal ganglia in MDD.

MR signal intensity of gray matter/white matter contrast and intracranial fat: effects of age and sex.

Signal intensity (SI) values of gray- and white-matter brain regions of interest (ROIs) were obtained from T(2)- and proton density-weighted magnetic resonance (MR) images of 58 normal subjects aged 22-82 years (31 females, 52.3+/-18.8 years; 27 males, 54.1+/-18.1 years). Sampled ROIs included the caudate, putamen, thalamus, orbitofrontal gyrus, gyrus rectus, uncus, frontal white matter, anterior and posterior corpus callosum, cranial-cervical junction fat, and retroorbital fat. Effects of age and sex on SI were examined using repeated-measures analysis of covariance. For both T(2)- and proton density-weighted acquisitions, a significant inverse relationship between age and SI was observed for the ratio of all summed gray-matter ROIs divided by summed white-matter ROIs. This relationship was additionally observed for ratios of both subcortical gray/white matter and cortical gray/white matter. Females compared with males had significantly lower cortical gray/white matter ratios on T(2)-weighted scans. Differences in SI were observed between cranial-cervical junction fat and retroorbital fat on both acquisitions, with females showing significantly higher values for cranial-cervical junction fat and males showing higher values for retroorbital fat. Implications for brain morphometry, the use of fat as a reference standard, and other issues in neuroimaging are discussed.