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Objective To examine the relationship of baseline clinical, radiographic, molecular and MRI measures with structural progression (subregional MRI-based femorotibial cartilage loss) in knee osteoarthritis (OA). Methods Single knees of 75 female participants with radiographic knee OA (and 77 healthy control participants) were examined over 24 months using MRI. Subregional femorotibial cartilage thickness was determined at baseline and follow-up. Baseline clinical, radiographic, molecular (n=16) and quantitative MRI-based measures of the meniscus and cartilage, including delayed gadolinium-enhanced MRI (dGEMRIC) and T2, were obtained. Differences in these baseline measures between radiographic osteoarthritic knees with longitudinal cartilage thinning (or thickening) and those with no significant change were evaluated by receiver operator characteristic analyses and Wilcoxon rank sum tests. Results The relatively strongest predictors of longitudinal cartilage thinning were reduced baseline cartilage thickness in the medial femur (area under the curve (AUC)=0.81), varus malalignment (AUC=0.77), reduced minimum joint space width and a greater radiographic joint space narrowing (JSN) score (both AUC=0.74). These remained significant after adjusting for multiple comparisons using false discovery rates. Reduced bone resorption (C-terminal telopeptide of type I collagen; AUC=0.65) and a low dGEMRIC index (reflecting low proteoglycan content) in the medial tibia (AUC=0.68) were associated with longitudinal cartilage thinning, but failed to reach statistical significance after correction for multiple testing in this (small) sample. Conclusions This exploratory study indicates that baseline molecular or MRI cartilage compositional markers may not provide better discrimination between knees with cartilage thinning and those without longitudinal change than simple radiographic measures, such as greater JSN score.

Obesity, as a primary risk factor for osteoarthritis (OA), has been shown to alter joint loading, but may also result in metabolic changes characterized by chronic, low-level inflammation due to increased circulating levels of adipose-derived cytokines, or "adipokines." The presence of the infrapatellar fat pad in the knee suggests that local changes in adipokine concentrations may influence knee OA. This study examined the hypotheses that the volume of the infrapatellar fat pad is correlated to the body mass index (BMI) of OA patients, and that fat pad volume is greater in subjects with OA. Fat pad volume was measured in sequential magnetic resonance (MR) images taken over one year in a cohort of 15 control and 15 knee OA subjects. No differences were observed in the fat pad volume between the two groups at baseline, 3, 6, or 12 months. In control subjects, no significant correlations were present between any parameters (age, BMI, weight, volume of fat pad at any time point). However, in the osteoarthritic group, fat pad volume was correlated with age at every time point. One possible explanation is that local factors related to knee OA may also induce enlargement of the fat pad with age. Alternatively, subjects who are prone to growth or enlargement of the fat pad may also be more prone to symptomatic OA. These findings provide intriguing preliminary data on the potential role of the infrapatellar fat pad in OA, although additional study is required to better understand the mechanisms of this relationship.

Summary Objective To identify subregional differences in femorotibial cartilage morphology between healthy controls and women with different grades of radiographic knee osteoarthritis (OA). Design 158 women aged ≥40 years were studied. Weight-bearing extended anterior-posterior (AP) and Lyon schuss radiographs were obtained and the Kellgren Lawrence grade (KLG) determined. 97 women had a body mass index (BMI)≤28, no symptoms, and were AP KLG0. 61 women had a BMI≥30, symptoms in the target knee, and mild (KLG2=31) to moderate (KLG3=30) medial femorotibial radiographic OA in the AP views. Coronal spoiled gradient echo water excitation sequences were acquired at 3.0 Tesla. Total plate and regional measures of cartilage morphology of the weight-bearing femorotibial joint were quantified. Results KLG2 participants displayed, on average, thicker cartilage than healthy controls in the medial femorotibial compartment (particularly anterior subregion of the medial tibia (MT) and peripheral [external, internal] subregions of the medial femur), and in the lateral femur. KLG3 participants displayed significantly thinner cartilage than KLG0 participants in the medial weight-bearing femur (central subregion), in the external subregion of the MT, and in the internal subregion of the lateral tibia. These differences were generally unaffected when possible effects of demographic covariates were considered. Conclusions The results indicate that in femorotibial OA regional cartilage thickening and thinning may occur, dependent on the (radiographic) disease status of the joint. These changes appear to display a heterogeneous spatial pattern, where certain subregions are more strongly affected than others.

Quantitative MRI (qMRI) of cartilage morphology is a promising tool for disease-modifying osteoarthritis drug (DMOAD) development. Recent studies at single sites have indicated that measurements at 3.0 Tesla (T) are more reproducible (precise) than those at 1.5 T. Precision errors and stability in multicentre studies with imaging equipment from various vendors have, however, not yet been evaluated.A total of 158 female participants (97 Kellgren and Lawrence grade (KLG) 0, 31 KLG 2 and 30 KLG 3) were imaged at 7 clinical centres using Siemens Magnetom Trio and GE Signa Excite magnets. Double oblique coronal acquisitions were obtained at baseline and at 3 months, using water excitation spoiled gradient echo sequences (1.0x0.31x0.31 mm3 resolution). Segmentation of femorotibial cartilage morphology was performed using proprietary software (Chondrometrics GmbH, Ainring, Germany).The precision error (root mean square coefficient of variation (RMS CV)%) for cartilage thickness/volume measurements ranged from 2.1%/2.4% (medial tibia) to 2.9%/3.3% (lateral weight-bearing femoral condyle) across all participants. No significant differences in precision errors were observed between KLGs, imaging sites, or scanner manufacturers/types. Mean differences between baseline and 3 months ranged from0.1% (non-significant) in the medial to 0.94% (p0.01) in the lateral femorotibial compartment, and were 0.33% (p0.02) for the total femorotibial subchondral bone area.qMRI performed at 3.0 T provides highly reproducible measurements of cartilage morphology in multicentre clinical trials with equipment from different vendors. The technology thus appears sufficiently robust to be recommended for large-scale multicentre trials.

This paper reviews published post-mortem brain and in-vivo proton magnetic resonance spectroscopy (1H-MRS) studies in Alzheimer's disease (AD) and focuses on the emerging role of N-acetylaspartate (NAA) as a prognostic marker of neuronal function. Post-mortem brain studies have reported significantly lower NAA levels in AD brains than in control brains, and some have correlated the low levels with neuropathological findings (i.e. amyloid plaques and neurofibrillary tangles). Similarly, almost all published in-vivo studies have reported lower NAA levels in AD patients compared to elderly controls. While some studies have found changes in metabolite levels that were considered useful for the diagnosis of AD, most have found that 1H-MRS provided little or no advantages over other, more common diagnostic tools. Instead, recent studies in AD and other neuropsychiatric disorders suggest that NAA may be more useful as a prognostic marker for monitoring neurodegeneration, stabilization, or improvement, and for evaluating therapeutic response to novel drugs.

Article abstract Hippocampal sulcal cavities are usually considered incidental findings on brain MRI. In a group of 92 elderly volunteers, the authors graded the number and size of hippocampal sulcal cavities with brain MRI to obtain a cavity score. Cavity scores increased with age, and were higher in subjects carrying the APOE ε4 or ε2 alleles than in subjects with the ε3/3 genotype. Age-related morphologic changes in the hippocampus may be mediated by the APOE genotype.

Four patients with cystic fibrosis (CF) were examined with combined hyperpolarized helium 3-enhanced and conventional proton magnetic resonance (MR) imaging. After inhalation of the polarized 3He gas, single breath-hold, gradient-echo images (resonant frequency of 3He) were obtained to depict lung ventilation. Conventional T2-weighted fast spin-echo (hydrogen) images were also obtained to depict morphologic abnormalities. 3He images were successfully and reproducibly generated that showed both morphologic abnormalities and, often more extensive, ventilation abnormalities. 3He MR imaging may provide a method for evaluating progression of pulmonary disease in patients with CF.

Non-ketotic hyperglycinaemia (NKH) is a rare, severe brain disease caused by deficient glycine cleavage enzyme complex activity resulting in elevated glycine concentrations. Recent experience suggests that factors in addition to glycine kinetics are involved in its pathogenesis. The glycine cleavage reaction through the formation of methylenetetrahydrofolate is an important one-methyl group donor. A deficiency in one-methyl group metabolites, in particular of choline, has been hypothesized in NKH. We investigated metabolites involved in one-methyl group metabolism in plasma and CSF of 8 patients with NKH, and monitored the effect of treatment with choline in one patient. Plasma and CSF choline and phosphatidylcholine concentrations were normal, except for a low plasma choline in the single neonate studied. Choline treatment did not change brain choline content, and was not associated with clinical or radiological improvement. Methionine concentrations and, in one-patient, S-adenosylmethionine and 5-methyltetrahydrofolate concentrations were normal in CSF. Homocysteine concentrations in CSF, however, were slightly but consistently elevated in all four patients examined, but cysteine, cysteinylglycine and glutathione were normal. Serine is important in the transfer of one-methyl groups from mitochondria to cytosol. Serine concentrations were normal in plasma and CSF, but dropped to below normal in CSF in three patients on benzoate treatment. These observations add to our understanding of the complex metabolic disturbances in NKH.

Two healthy volunteers who had inhaled approximately 0.75 L of laser-polarized helium-3 gas underwent magnetic resonance imaging at 1.5 T with fast gradient-echo pulse sequences and small flip angles ( < 10 degrees). Thick-section (20 mm) coronal images, time-course data (30 images collected every 1.8 seconds), and thin-section (6 mm) images were acquired. Subjects were able to breathe the gas (12% polarization) without difficulty. Thick-section images were of good quality and had a signal-to-noise ratio (S/N) of 32:1 near the surface coil and 16:1 farther away. The time images showed regional differences, which indicated potential value for quantitation. High-resolution images showed greater detail and a S/N of approximately 6:1.

The application of proton (1H) magnetic resonance spectroscopic imaging (MRSI) allows for noninvasive, localized analyses of brain biochemistry; however, minimal work has been devoted to the evaluation of 1H MRSI reproducibility. This study examined the reproducibility of 1H MRSI from five normal subjects on two occasions, separated by 10 days. Reproducibility of the MR signal was evaluated in the context of automated shimming, automated processing, and accurate subject repositioning. Reliability measures for physicochemical indices (choline moieties, creatine, N-acetylaspartate, and myo-inositol) were moderately concordant across repeat studies. Gain variation and repositioning results were excellent. It has been concluded that 1H MRSI reproducibility is adequate for serial studies of brain metabolism.

We evaluated the use of hyperglycaemia to reduce tumour pH in dog with spontaneous tumours. Dogs were randomized to two groups: control and glucose. Intravenous administration of 20% glucose was used to induce and maintain hyperglycaemia. Extra- and intracellular tumour pH were measured using interstitial pH microelectrodes and 31P-MRS, respectively. During the administration of glucose, the mean (+/- SEM) blood glucose concentration was 419.8 (+/- 32.8) and 121.1 (+/- 8.0) mg/dl for the glucose and control groups, respectively. The mean extracellular tumour pH before and following 90 min of hyperglycaemia was 7.15 (+/- 0.08) and 7.15 (+/- 0.09). During consecutive measurements, intracellular tumour pH did not change significantly for the control group or the group subjected to hyperglycaemic manipulation. In contradistinction to previous rodent studies, our results demonstrate that hyperglycaemia alone is not sufficient to manipulate either intra- (pHi) or extracellular (pHe) hydrogen ion concentration in spontaneous canine soft tissue tumours.

Objective:Cartilage morphology displays sensitivity to change in osteoarthritis (OA) with quantitative MRI (qMRI). However, (sub)regional cartilage thickness change at 3.0 Tesla (T) has not been directly compared with radiographic progression of joint space narrowing in OA participants and non-arthritic controls.Methods:A total of 145 women were imaged at 7 clinical centres: 86 were non-obese and asymptomatic without radiographic OA and 55 were obese with symptomatic and radiographic OA (27 Kellgren–Lawrence grade (KLG)2 and 28 KLG3). Lyon–Schuss (LS) and fixed flexion (FF) radiographs were obtained at baseline, 12 and 24 months, and coronal spoiled gradient echo MRI sequences at 3.0 T at baseline, 6, 12 and 24 months. (Sub)regional, femorotibial cartilage thickness and minimum joint space width (mJSW) in the medial femorotibial compartment were measured and the standardised response means (SRMs) determined.Results:At 6 months, qMRI demonstrated a −3.7% “annualised” change in cartilage thickness (SRM −0.33) in the central medial femorotibial compartment (cMFTC) of KLG3 subjects, but no change in KLG2 subjects. The SRM for mJSW in 12-month LS/FF radiographs of KLG3 participants was −0.68/−0.13 and at 24 months was −0.62/−0.20. The SRM for cMFTC changes measured with qMRI was −0.32 (12 months; −2.0%) and −0.48 (24 months; −2.2%), respectively.Conclusions:qMRI and LS radiography detected significant change in KLG3 participants at high risk of progression, but not in KLG2 participants, and only small changes in controls. At 12 and 24 months, LS displayed greater, and FF less, sensitivity to change in KLG3 participants than qMRI.

Objective: The Lyon Schuss (LS) and fixed flexion (FF) views of the knee are superior to a conventional standing anteroposterior view in evaluating joint space narrowing (JSN) in osteoarthritis (OA). Both position the knee identically but only the LS aligns the medial tibial plateau (MTP) with the x -ray beam fluoroscopically. The present study provides the first head-to-head comparison of the LS and FF views. Methods: At baseline and 12 months, 62 OA and 99 control knees were imaged twice on the same day with LS and FF views. Minimum joint space width (mJSW) was measured by computer and MTP alignment was assessed from the distance between anterior and posterior margins of the MTP (intermargin distance, IMD). Reproducibility of measurements of mJSW and sensitivity to change were evaluated. Results: In normal knees, JSW did not vary over 12 months with either view. In OA knees, 12-month mJSN was 0.22 (0.43) mm with the LS view and −0.01 (0.46) mm with the FF view (p = 0.0002 and p = 0.92, respectively). Mean IMD was only half as large in LS as in FF views (0.9 (0.5) mm vs 1.9 (1.2) mm, p Conclusions: LS and FF radiographs offer similar reproducibility in JSW measurement. However, presumably due to its superiority in aligning the MTP, the LS view is much more sensitive to JSN in OA knees.

Regional variations in metabolic parameters derived with multivoxel, localized phosphorus-31 magnetic resonance (MR) spectroscopy in spontaneous human-soft-tissue sarcomas were compared with variations in the same parameters in normal human legs. In addition, multivoxel P-31 MR spectroscopy of transplanted rodent sarcomas and microelectrode measurement of pH and PO2 in several locations within them were performed, and, when appropriate, results were compared with the clinical data. Striking voxel-voxel variability in parameters derived with P-31 spectroscopy was found in tumors, with less marked variability seen in normal legs. In the rodent tumors, spatial variations also were found in pH and PO2 measured by means of microelectrodes. These data are consistent with the results of regional measurements in tumors by means of other methods and suggest that clinical MR spectroscopic studies of tumors may need to consider the variability within malignant lesions.

The authors studied the usefulness of hydrogen-1 T2 measurements and phosphorus-31 magnetic resonance (MR) spectroscopy as indicators of prognosis and monitors of response to therapy in a group of patients with soft-tissue sarcomas. All eight patients were treated with combined local hyperthermia and fractionated radiation therapy, followed by surgical resection of the tumor. Each patient underwent T2 measurements and five patients underwent MR spectroscopy (phase encoded in one dimension) before treatment, after the first hyperthermia treatment, at the end of the therapy course, and just before surgery. Catheter thermometry was performed at each hyperthermia treatment. The T2 and MR spectroscopic variables were compared with thermometric data and the histologic findings from the complete surgical specimen. Changes in T2 correlated with histologic grade of tumor and thermometric data. The pretherapy tumor pH correlated positively, and changes during therapy in pH, ratio of phosphocreatine to inorganic phosphate (Pi), ratio of nucleoside triphosphate to Pi, and the phosphomonoester signal-to-noise ratio correlated negatively, with the percentage of tumor necrosis on the surgical specimen. These preliminary data suggest MR imaging and MR spectroscopy may be useful in the evaluation of such patients before and during therapy.

The authors aimed to use baseline data of an ongoing large, prospective study in subjects with mild cognitive impairment (MCI) to investigate the impact of APOE genotype on the symptom profile of the condition.Cognitive assessments included the AD Assessment Scale cognitive subscale (ADAS-cog), the Mini-Mental State Examination (MMSE), and a cognitive battery for assessment of memory, attention, and executive function. Behavioral assessments included the Neuropsychiatric Inventory and Beck Depression Inventory. Activities of daily living were assessed by the AD Cooperative Study Activities of Daily Living (ADCS-ADL) scale. Hippocampal volumes were measured with MRI.A total of 494 of 1,018 study subjects provided APOE data. Approximately 40% of the subjects were APOE epsilon4 carriers. APOE epsilon4 carriers had lower MMSE (p = 0.01) and higher ADAS-cog (p0.0001) scores than noncarriers, indicating worse cognitive impairment. APOE epsilon4 carriers also had greater deficits on New York University delayed paragraph recall and Buschke free and cued selective reminding tests, and on the ADCS-ADL scale (p0.001). They also had smaller hippocampal volumes (p = 0.002). Behavioral scores were similar across the subgroups.MCI subjects carrying the APOE epsilon4 allele showed distinct cognitive and imaging profiles, which appeared to resemble those of early Alzheimer patients. APOE epsilon4 genotype was associated with greater impairments in memory and functional activities as well as hippocampal atrophy.

OBJECTIVE: Bronchiolitis obliterans syndrome is the major cause of long-term graft failure in lung transplant recipients and may be partially reversible if diagnosed early and treated. Diagnosis is difficult because findings of transbronchial biopsy are often negative in patients with early disease. We are investigating a novel MR ventilation agent, hyperpolarized 3He, for evaluating ventilatory abnormalities in lung transplant recipients with suspected bronchiolitis obliterans syndrome. CONCLUSION: In this preliminary study, the extent of ventilatory defects revealed on 3He-enhanced MR images correlated with severity of bronchiolitis obliterans syndrome using an established clinical grading system. This new technique may hold potential for diagnosing bronchiolitis obliterans syndrome in lung transplant recipients.

The adverse prognostic impact of tumor hypoxia has been demonstrated in human malignancy. We report the effects of radiotherapy and hyperthermia (HT) on soft tissue sarcoma oxygenation and the relationship between treatment-induced changes in oxygenation and clinical treatment outcome. Patients receiving preoperative radiotherapy and HT underwent tumor oxygenation measurement pretreatment after the start of radiation/pre-HT and one day after the first HT treatment. The magnitude of improvement in tumor oxygenation after the first HT fraction relative to pretreatment baseline was positively correlated with the amount of necrosis seen in the resection specimen. Patients with90% resection specimen necrosis experienced longer disease-free survival than those withor = 90% necrosis. Increasing levels of tumor hypoxia were also correlated with diminished metabolic status as measured by P-31 magnetic resonance spectroscopy.

The purpose of this study was to investigate the potential role of FDG-PET in the monitoring of neoadjuvant therapy of soft-tissue and musculoskeletal sarcomas.Nine patients were studied. Neoadjuvant therapy consisted of either chemotherapy or combined radiotherapy and hyperthermia. The FDG-PET studies were obtained, when possible, prior to therapy, 1-3 wk after commencement of therapy, and prior to surgery after completion of neoadjuvant therapy. In two patients, all three studies were completed. The remainder of patients underwent one or two studies at varying timepoints.In tumors treated with combined radiotherapy and hyperthermia, well-defined regions of absent uptake developed within responsive tumors, correlating pathologically with necrosis. Following treatment, a peripheral rim of FDG accumulation was found to correlate pathologically with the formation of a fibrous pseudocapsule. In tumors treated with chemotherapy, FDG accumulation decreased more homogeneously throughout the tumor, in responsive cases. Despite 100% tumor cell kill in some patients, persistent tumor FDG uptake was observed which correlated pathologically with uptake within benign therapy-related fibrous tissue. Significant FDG accumulation was also observed at the site of an uncontaminated incisional biopsy.These initial results demonstrate changes in tumor accumulation of FDG during and after neoadjuvant therapy; these changes are dependent on the type of neoadjuvant therapy administered. Prominent FDG accumulation was observed in benign tissues both within and adjacent to the treated tumor.

1. Although dementia is caused by a heterogeneous group of diseases and pathologic states, Alzheimer's disease is the largest cause, estimated to account for 50 to 75% of all dementias. 2. Unfortunately, confirmation of Alzheimer's disease (AD) requires postmortem histologic confirmation; clinical diagnosis prior to death remains one of exclusion. 3. A large number of structural and volumetric MRI studies have noted anatomic and structural changes accompanying AD, including variable degrees of general cortical atrophy. 4. A classic feature reported by many MRI studies is hippocampal and temporal lobe atrophy. 5. White matter hyperintensities on MRI are common, especially in late onset AD although their significance is still controversial. 6. This article reviews the contribution of magnetic resonance to imaging the neuropathologic changes of AD, discussing both advantages and limitations, and summarizing the major findings.

The present study was designed to compare evaluation of skeletal muscle metabolism (vastus lateralis) evaluated by 31P-magnetic resonance spectroscopy (MRS) and biochemical analysis. During identical isometric knee extensor exercise protocols to fatigue in eight men, biopsy samples were taken at rest, peak exercise, and 32 s postexercise and 31P-MRS data were collected continuously for phosphocreatine (PCr), pH, ATP, and P(i) at 8- or 32-s intervals. There was no difference in ATP or pH measurements between the two techniques at rest, during peak exercise, or in recovery. Corresponding measurements of pH by the two techniques were closely related (r = 0.88, P < 0.01), and pH measured by 31P-MRS was closely related to muscle lactate accumulation (r = -0.84, P < 0.001). The level of PCr at peak exercise, expressed as a percentage of the baseline value, was not different between the two techniques (42 +/- 15 vs. 46 +/- 15%). The results indicate that, in skeletal muscle in normal subjects, 1) measurements of pH and PCr at rest and during exercise do not differ between the 31P-MRS and biopsy techniques and 2) muscle pH measured by 31P-MRS is closely related to lactate accumulation in men. Our data suggest that direct comparison of results of studies of exercise metabolism using these two techniques is warranted.

Proton localized magnetic resonance spectroscopy was studied in 20 social phobics and 20 age- and sex-matched controls. Stimulated Echo Acquisition Mode volume element localization was used with chemical shift imaging. Choline and creatine signal-to-noise ratios (SNRs) were significantly lower in social phobia than in controls in subcortical, thalamic, and caudate areas. In the social phobic group, N-acetylaspartate (NAA) SNR was significantly lower in cortical and subcortical regions, and ratios of NAA to other metabolites were lower in social phobia. Choline, creatine, and NAA SNRs were inversely correlated to total social phobia and fear symptoms, as measured by the Brief Social Phobia Scale, in the thalamic and noncortical gray areas. In a small number of patients who received clonazepam, posttreatment SNRs generally increased relative to baseline. Our results suggest a promising place for magnetic resonance spectroscopy in social phobia and also indicate potential pharmacodynamic uses of this technique.

• We obtained oxygen measurements from a human eye that contained small preretinal droplets of perfluorotributylamine (FTBA) by using fluorine-19 magnetic resonance spectroscopy. These droplets were the remainder of a larger volume of FTBA that was used as an intraoperative retinal tamponade during retinal detachment repair. The spin-lattice relaxation rate ([T 1 ] -1 ) of the FTBA fluorine nuclide was obtained that could then be related, by direct proportionality, to droplet Po 2 . With the patient in a supine position, the droplets could be positioned over the macula in the preretinal vitreous space, whereon the FTBA Po 2 could be influenced by the preretinal oxygen concentration. Preretinal Po 2 values, derived from magnetic resonance spectroscopy, were in the range of 6 to 9 mm Hg, although multiple components were identified that were suggestive of a heterogeneous distribution of Po 2 values in the population of droplets. To our knowledge, this investigation is the first to demonstrate the feasibility of this approach to performing long-term, noninvasive preretinal oxygen measurements in the vitrectomized human eye by using small droplets of a liquid perfluorochemical.

Using 31P spectroscopy and magnetic resonance imaging (MRI), the authors studied changes in muscle phosphorous metabolites and T2 with isometric knee extension to evaluate the potential role of T2 images in coil placement for exercise spectroscopy studies. Increased signal intensity was visible in active muscles on T2 images after exercise. Calculated T2-weighted values were elevated immediately after exercise in the quadriceps (P less than .01). T2 increases for individual quadricep muscles varied, with the largest changes in the rectus femoris and the least in the vastus lateralis. 31P spectroscopy studies demonstrated similar findings: percent change in T2 correlated positively with inorganic phosphorus to phosphocreatine ratio (Pi/PCr) (r = 0.89, P less than .01) and negatively with pH (r = -0.88, P less than .01). The correlations between imaging and spectroscopy suggest that T2 images may allow more precise placement of phosphorous coils in exercise studies. The heterogeneity of T2 changes within the quadriceps with exercise suggests that assumptions about muscle activity may be misleading. T2 images may provide muscle activity verification for exercise studies.

We evaluated the role of 31P MR spectroscopy in the diagnosis of renal transplant allograft dysfunction. Thirty-six 31P MR spectroscopy examinations were prospectively performed in 35 patients with renal allografts. The study was performed in two phases. In the first phase, 12 transplant recipients with normal graft function were studied as normal controls. During phase two, 24 31P MR spectroscopy studies were performed in patients at the time of renal transplant biopsy for allograft dysfunction. Twenty-one of these studies were technically adequate. Pathologic analysis of the biopsy specimens showed evidence of allograft rejection in 14 and no rejection in seven. Various phosphorus metabolite ratios were calculated for each patient, including phosphodiesters/phosphomonoesters (PDE/PME), phosphomonoesters/inorganic phosphate (PME/Pi), and inorganic phosphate/adenosine triphosphate (Pi/ATP). The PDE/PME and Pi/ATP ratios in the allografts with rejection differed significantly from the corresponding metabolite ratios in patients without rejection (p = .017 and p = .024, respectively). A PDE/PME ratio exceeding 0.8 had a sensitivity of 100% and specificity of 86% for predicting rejection. A Pi/ATP ratio greater than 0.6 had a sensitivity of 72% and a specificity of 86% for predicting rejection. We conclude that 31P MR spectroscopy may be useful as a noninvasive method for evaluating renal metabolism during episodes of transplant allograft dysfunction.

Recent reports have suggested that recurrent tumors can be differentiated from posttreatment fibrosis by use of T2weighted MR imaging [1 -5]. Fibrosis has been shown to have low signal intensity on such images [1-5] and to be distinguishable statistically from recurrent tumor on this basis [4, 5]. Fibrosis in patients 1 year or more after therapy, in particular, has been well differentiated from recurrent tumor [5]. However, not all authors have reported such good results [6], and it appears that other abnormalities such as inflammation and necrosis can produce changes on MR images that are indistinguishable from recurrent tumor [3, 5, 6]. The metabolic information provided by 31P MR spectroscopy seems potentially useful in differentiation of recurrent tumor from nonneoplastic entities. We report a case that exemplifies this possibility.

It is a requirement of many localized NMR spectroscopy experiments, such as DRESS, that collection of the free induction decay be delayed a significant time after the middle of the last pulse. This leads to distortion of the spectra and seriously impedes the retrieval of quantitative information from these spectra. A technique is described in which a correction function is derived from the convoluted spectrum and is used to produce a spectrum with much reduced distortion from which quantitative information may easily be obtained by conventional techniques. © 1988 Academic Press, Inc.

The gold-aluminum intermetallic phases are known to contribute to the long term degradation of gold wire ball bonds to aluminum metallization on semiconductor devices. The properties of these intermetallics were investigated through two techniques: 1) ball bond shear testing and 2) preparation of known intermetallic compositions by using thin film Au-Al diffusion couples. The influence of thermal aging on gold ball bonds attached to aluminum metallization (on both Si and SiO 2 ) was determined through ball shear measurements. The strength of gold wire bonds made to films of Au-Al intermetallics was similarly measured. Failure mode analyses of the sheared bonds for the various systems examined are presented. The effect of a nondestructive ball shear test on the ultimate ball shear strength is given. Ultraviolet (UV)-ozone cleaning of the aluminum prior to gold wire bonding is discussed in light of Auger spectroscopy of the aluminum oxide formed on the surface. The effect of shearing direction relative to the direction of the ultrasonic scrubbing was also examined.

• In a cross-sectional study, 34 diabetic patients with clinically significant macular edema underwent visual acuity testing, stereo fundus photography (graded for retinal thickening and hard exudates), fluorescein angiography (evaluated for macular leakage and the outline of the foveal avascular zone [FAZ]), and vitreous fluorophotometry (whereby posterior penetration ratios were calculated). This last ratio provided the highest single correlation with visual acuity; next highest were patient age and FAZ grading. Multivariate regression confirmed that these three variables together best predicted visual acuity. Lesser correlations with acuity were obtained with angiographic leakage and fundus photography grading. Cross-correlations among all gradings showed that indicators of breakdown of the blood-retinal barrier, ie, fluorophotometry, angiographic leakage, and retinal thickening, were significantly correlated with each other, whereas FAZ grading was independent of all these factors and correlated only with acuity. By performing vitreous fluorophotometry and fluorescein angiography, it is possible to quantitate two major components of diabetic maculopathy: breakdown of the blood-retinal barrier and macular ischemia, both of which are highly correlated with visual acuity.

A section-selective three-dimensional phosphorus-31 chemical shift imaging (CSI) experiment was evaluated as the spatial localization method for spectroscopy in an integrated clinical magnetic resonance (MR) imaging and spectroscopy examination. The results of a CSI experiment can be displayed as either spectra related to specific voxels or "metabolite maps," in which the relative concentration of a given metabolite is displayed as an overlay of the MR image. This method was applied to the study of a soft-tissue mass and to a meningioma. The total imaging time in each case was 17 minutes with a voxel size of 27 cm3 in the extremity and 64 cm3 in the brain. The total time to set up this part of the study was about 10 minutes. No additional shimming was necessary when the center of the field of view selected for the CSI experiment was located at or near isocenter. The promising results obtained with this approach make the CSI method an attractive choice of spatial localization method.

A Sargon user-defined Octopus program was devised to quantitate central visual field changes following laser photocoagulation for choroidal neovascular membranes. The program was found to be reliable in testing the nine patients studied. All patients had areas of improved and areas of reduced sensitivity. The areas of reduced sensitivity were larger than the areas of improved sensitivity (P less than 0.05), with a net negative change in sensitivity found in all cases. However, the improved areas tended to be closer to fixation than the worsened areas. Quantitative static perimetry can be applied to the study of choroidal neovascular membranes. It is an important visual parameter that should be evaluated in future studies of these membranes, especially with regard to wavelength efficacy in photocoagulation therapy.

SummaryObjectiveThis study evaluated the longitudinal performance of a modified Lyon schuss (LS) knee examination in the detection of radiographic joint space narrowing (JSN) in knees with osteoarthritis (OA). The modified LS exam entails two to four iterative acquisitions with empirically adjusted angulation of the X-ray beam to achieve superimposition of the anterior and posterior margins of the medial tibial plateau (MTP), a marker of parallel radioanatomic alignment that the original LS exam achieves with fluoroscopically guided beam angulation.MethodsSeventy-four obese women with symptomatic knee OA underwent LS and fixed-flexion (FF, caudal 10° beam angulation) X-ray exams at baseline and 1 year later. For 47 subjects, beam angulation for both LS exams was guided by fluoroscopy. For 27 subjects, the modified LS exam was performed at one or both times. Modified and original LS procedures were evaluated relative to concurrent FF radiographs with respect to the inter-margin distance (IMD) at the MTP midpoint (quality and reproducibility of alignment) and sensitivity to JSN.ResultsCompared to FF radiographs, modified LS radiographs afforded a smaller mean IMD at baseline (0.89 vs 2.06mm, P=0.002), more reproducible IMD (mean change=0.49 vs 0.91mm, P=0.007) and more rapid JSN (mean=0.25 vs 0.02mm/yr, P=0.005). These differences paralleled those observed between original LS and FF procedures with respect to baseline alignment (0.96 vs 1.94mm, P

The purpose of this study is the evaluation of clinical utility of phosphorous chemical shift imaging (31P CSI) of neoplastic disease. The current role of 31P CSI can be considered twofold, the differentiation of tumor from non-tumor in diagnosis and the evaluation of neoplastic therapy by serial monitoring of localized 31P information from neoplastic lesions.

Phosphorus (31P) spectroscopic images showing the distribution of high-energy phosphate metabolites in the human brain have been obtained at 1.5 T in scan times of 8.5 to 34 min at 27 and 64 cm3 spatial resolution using pulsed phase-encoding gradient magnetic fields and three-dimensional Fourier transform (3DFT) techniques. Data were acquired as free induction decays with a quadrature volume NMR detection coil of a truncated geometry designed to optimize the signal-to-noise ratio on the coil axis on the assumption that the sample noise represents the dominant noise source, and self-shielded magnetic field gradient coils to minimize eddy-current effects. The images permit comparison of metabolic data acquired simultaneously from different locations in the brain, as well as metabolite quantification by inclusion of a vial containing a standard of known 31P concentration in the image array. Values for the NMR visible adenosine triphosphate in three individuals were about 3 mM of tissue. The ratio of NMR detectable phosphocreatine to ATP in brain was 1.15 ± 0.17 SD in these experiments. Potential sources of random and systematic error in these and other 31P measurements are identified. © 1988 Academic Press, Inc.

Male cats were anesthetized with pentobarbital. In one series of experiments a Foley catheter was placed suprapubically in the urinary bladder and physiologic saline, under a constant head of pressure, was allowed to flow at a constant rate through the bladder. Alpha-adrenergic stimulants such as ephedrine, norepinephrine, or methoxamine all caused a decrease or cessation in urinary flow. This effect was reversed by the alpha-adrenergic blocking agent, phentolamine. In addition, phentolamine administration caused penile erection. Erection also occurred after administration of the alpha-adrenergic blocking agent, phenoxybenzamine, or the beta2-adrenergic stimulants terbutaline or salbutamol. In each case the erection could be reversed, and usually terminated completely, by administration of the beta-adrenergic blocking agent, propranolol. Hypotension per se was not the required event to initiate erection because administration of acetylcholine, histamine, or prostaglandin E2 did not result in penile erection. In two of five experiments nitroprusside caused an erection. It was concluded that a predominance of beta2 activity in the penile vasculature is involved in erection.

As a continuation of our efforts to develop and study inhibitors which act presynaptically on neuromuscular function, sulfur analogues of hemicholinium-3 (HC-3, 1) and acetyl-seco-hemicholinium-3 (AcHC-3, 3) were prepared. In each case sulfur is substituted for the noncarbonyl oxygen in HC-3 (1) and AcHC-3 (3). As expected on the basis of conformational differences between acetylcholine and acetylthiocholine both of the thio analogues are produced in the seco form and do not cyclize spontaneously or when subjected to aqueous, acidic conditions up to 100 degrees C. Both compounds are stable in aqueous pH 7.4 solutions at 37 degrees C and in slightly acidic D2O solutions for more than 24 h. While thio-seco-hemicholinium 3 (11) is stable in the presence of acetylcholinesterase and butyrylcholinesterase in H2O at pH 7.4, acetylthio-seco-hemicholinium-3 (12) reacts within seconds to form the hemiacetal form of thiohemicholinium-3 (16). Mouse toxicity studies (LD50) indicate that while 12 is approximately as toxic as HC-3 (1) and AcHC-3 (3), 11 is 226 times less toxic. As in the studies with 1 and 3, mice were protected from 11 by choline and slightly by neostigmine. It is of interest, however, that almost equal and intermediate protection against 12 was afforded by choline and neostigmine. Structure-toxicity relationships of 1,3,11, 12, and 16 are discussed.

A footplate of an anterior chamber lens that extruded through clear cornea was treated by severing the protruding haptic with the Nd:YAG laser and removing it surgically. During the procedure, the remainder of the implant was repositioned and vitreous traction was relieved by pars plana vitrectomy. This technique appeared less injurious to the eye than attempting to cut all four fibrosed haptics and remove the entire implant.

• We obtained electroretinograms (ERGs) from normal subjects and from patients with sickle cell disease. The ERG components (a-wave, b-wave, and oscillatory potentials) obtained from normal subjects and patients without peripheral retinal neovascularization did not differ in either amplitude or implicit time. However, ERG components obtained from patients with peripheral retinal neovascularization were reduced in amplitude compared with those obtained from normal subjects or patients without neovascularization. The reduced a-wave, b-wave, and oscillatory potential amplitudes may have been due to photoreceptor dysfunction secondary to choroidal ischemia or possibly increased oxygen demands by the inner retina. Ischemia of the inner retina may also have contributed to the altered b-wave and oscillatory potentials. These results suggest that ERG provides a means of assessing the consequence of peripheral retinal ischemia to retinal cell function and could be of value in monitoring patients with sickle cell disease for the development of clinically significant peripheral retinal neovascularization.

Chorioretinal lesions produced by dye laser photocoagulation were examined on normal monkey retinas, using angiographic and histopathologic techniques. Retinal burns produced by green (514 nm), yellow (577 nm), orange (600 nm), and red (630 nm) laser lights were placed in the posterior pole between the fovea and the major vascular arcades. When examined histopathologically 24 hours after treatment, greater damage to the inner retina and deep choroid was noted with the red laser light than with the green, yellow and orange laser lights. These differences were not detectable 31 days after treatment. There were no appreciable acute differences among the lesions caused by green, yellow and orange irradiation. Laser light at four wavelengths of the orange spectrum (590, 595, 600, and 605 nm) produced comparable chorioretinal destruction in the juxtafoveal zone when examined 24 hours and 31 days after treatment. Retinal arterioles and venules treated with yellow (577 nm) and orange (600 nm) laser light demonstrated endothelial and pericytic cell damage. Changes in the outer retina, pigment epithelium, and choriocapillaris were also present beneath the photocoagulated vessels.