Predictors of visceral and subcutaneous adipose tissue and muscle density: The ShapeUp! Kids study.

BACKGROUND AND AIMS: Body fat distribution, i.e., visceral (VAT), subcutaneous adipose tissue (SAT) and intramuscular fat, is important for disease prevention, but sex and ethnic differences are not well understood. Our aim was to identify anthropometric, demographic, and lifestyle predictors for these outcomes. METHODS AND RESULTS: The cross-sectional ShapeUp!Kids study was conducted among five ethnic groups aged 5-18 years. All participants completed questionnaires, anthropometric measurements, and abdominal MRI scans. VAT and SAT areas at four lumbar levels and muscle density were assessed manually. General linear models were applied to estimate coefficients of determination (R2) and to compare the fit of VAT and SAT prediction models. After exclusions, the study population had 133 male and 170 female participants. Girls had higher BMI-z scores, waist circumference (WC), and SAT than boys but lower VAT/SAT and muscle density. SAT, VAT, and VAT/SAT but not muscle density differed significantly by ethnicity. R2 values were higher for SAT than VAT across groups and improved slightly after adding WC. For SAT, R2 increased from 0.85 to 0.88 (girls) and 0.62 to 0.71 (boys) when WC was added while VAT models improved from 0.62 to 0.65 (girls) and 0.57 to 0.62 (boys). VAT values were significantly lower among Blacks than Whites with little difference for the other groups. CONCLUSION: This analysis in a multiethnic population identified BMI-z scores and WC as the major predictors of MRI-derived SAT and VAT and highlights the important ethnic differences that need to be considered in diverse populations.

Body Fat Distribution, Glucose Metabolism, and Diabetes Status Among Older Adults: The Multiethnic Cohort Adiposity Phenotype Study.

BACKGROUND: As the proportion of visceral (VAT) to subcutaneous adipose tissue (SAT) may contribute to type 2 diabetes (T2D) development, we examined this relation in a cross-sectional design within the Multiethnic Cohort that includes Japanese Americans known to have high VAT. The aim was to understand how ectopic fat accumulation differs by glycemic status across ethnic groups with disparate rates of obesity, T2D, and propensity to accumulate VAT. METHODS: In 2013-2016, 1,746 participants aged 69.2 (standard deviation, 2.7) years from five ethnic groups completed questionnaires, blood collections, and whole-body dual X-ray absorptiometry and abdominal magnetic resonance imaging scans. Participants with self-reported T2D and/or medication were classified as T2D, those with fasting glucose >125 and 100-125 mg/dL as undiagnosed cases (UT2D) and prediabetes (PT2D), respectively. Using linear regression, we estimated adjusted means of adiposity measures by T2D status. RESULTS: Overall, 315 (18%) participants were classified as T2D, 158 (9%) as UT2D, 518 (30%) as PT2D, and 755 (43%) as normoglycemic (NG), with significant ethnic differences (P < 0.0001). In fully adjusted models, VAT, VAT/SAT, and percent liver fat increased significantly from NG, PT2D, UT2D, to T2D (P < 0.001). Across ethnic groups, the VAT/SAT ratio was lowest for NG participants and highest for T2D cases. Positive trends were observed in all groups except African Americans, with highest VAT/SAT in Japanese Americans. CONCLUSION: These findings indicate that VAT plays an important role in T2D etiology, in particular among Japanese Americans with high levels of ectopic adipose tissue, which drives the development of T2D to a greater degree than in other ethnic groups.

MRI default mode network connectivity is associated with functional outcome after cardiopulmonary arrest.

BACKGROUND: We hypothesized that the degree of preserved functional connectivity within the DMN during the first week after cardiopulmonary arrest (CPA) would be associated with functional outcome at hospital discharge. METHODS: Initially comatose CPA survivors with indeterminate prognosis at 72 h were enrolled. Seventeen CPA subjects between 4 and 7 days after CPA and 17 matched controls were studied with task-free fMRI. Independent component analysis was performed to delineate the DMN. Connectivity strength in the DMN was compared between CPA subjects and controls, as well as between CPA subjects with good outcome (discharge Cerebral Performance Category or CPC 1-2) and those with bad outcome (CPC 3-5). The relationship between connectivity strength in the posterior cingulate cortex (PCC) and precuneus (PC) within the DMN with discharge CPC was evaluated using linear regression. RESULTS: Compared to controls, CPA subjects had significantly lower connectivity strength in subregions of the DMN, the PCC and PC (p < 0.0001). Furthermore, connectivity strength in the PCC and PC was greater in CPA subjects with good outcome (n = 8) than those with bad outcome (n = 9) (p < 0.003). Among CPA subjects, the connectivity strength in the PCC and PC showed strong linear correlations with the discharge CPC (p < 0.005). CONCLUSIONS: Among initially comatose CPA survivors with indeterminate prognosis, task-free fMRI demonstrated graded disruption of DMN connectivity, especially in those with bad outcomes. If confirmed, connectivity strength in the PC/PCC may provide a clinically useful prognostic marker for functional recovery after CPA.

Subcutaneous and visceral fat assessment by DXA and MRI in older adults and children.

OBJECTIVE: Given the importance of body fat distribution in chronic disease development, feasible methods to assess body fat are essential. This study compared dual-energy x-ray absorptiometry (DXA) in measuring visceral and subcutaneous adipose tissue (VAT and SAT) with magnetic resonance imaging (MRI). METHODS: VAT and SAT were assessed using similar DXA and MRI protocols among 1,795 elderly participants of the Adiposity Phenotype Study (APS) and 309 children/adolescents in Shape Up! Kids (SKids). Spearman correlations, Bland-Altman plots, and coefficients of determination (R2 ) assessed agreement between DXA and MRI measures. RESULTS: DXA overestimated SAT values in APS (315 vs. 229 cm2 ) and SKids (212 vs. 161 cm2 ), whereas DXA underestimated VAT measures (141 vs. 167 cm2 ) in adults only. The correlations between DXA and MRI values were stronger for SAT than VAT (APS: r = 0.92 vs. 0.88; SKids: 0.90 vs. 0.74). Bland-Altman plots confirmed better agreement for SAT than VAT despite differences by sex, ethnicity, and weight status with respective R2 values for SAT and VAT of 0.88 and 0.84 (APS) and 0.81 and 0.69 (SKids). CONCLUSION: These findings indicate that SAT by DXA reflects MRI measures in children and older adults, whereas agreement for VAT is weaker for individuals with low VAT levels.

Predictors of liver fat among children and adolescents from five different ethnic groups.

OBJECTIVES: As rates of obesity around the world have increased, so has the detection of high level of liver fat in children and adolescents. This may put them at risk for cardiovascular disease later in life. This analysis of a cross-sectional population-based study of children and adolescents evaluated demographic and lifestyle determinants of percent liver fat. METHODS: Healthy participants (123 girls and 99 boys aged 5-17 years) recruited by convenience sampling in three locations completed questionnaires, anthropometric measurements, and dual X-ray absorptiometry and magnetic resonance imaging (MRI) assessment. General linear models were applied to estimate the association of demographic, anthropometric, and dietary factors as well as physical activity with MRI-based percent liver fat. RESULTS: The strongest predictor of liver fat was body mass index (BMI; p < 0.0001); overweight and obesity were associated with 0.5% and 1% higher liver fat levels. The respective adjusted mean percent values were 2.9 (95% CI 2.7, 3.1) and 3.4 (95% CI 3.2, 3.6) as compared to normal weight (2.4; 95% CI 2.3, 2.6). Mean percent liver fat was highest in Whites and African Americans, intermediate in Hispanic, and lowest among Asians and Native Hawaiians/Pacific Islanders (p < 0.0001). Age (p = 0.67), sex (p = 0.28), physical activity (p = 0.74), and diet quality (p = 0.70) were not significantly related with liver fat. CONCLUSIONS: This study in multiethnic children and adolescents confirms the strong relationship of BMI with percent liver fat even in a population with low liver fat levels without detecting an association with age, sex, and dietary or physical activity patterns.

Biomarker-based visceral adiposity score and incident type 2 diabetes in the multiethnic cohort.

PURPOSE: Visceral adipose tissue (VAT) may be more important than subcutaneous fat in type 2 diabetes (T2D) etiology. We examined a VAT score developed in reference to MRI measurement of VAT in the Multiethnic Cohort (MEC) as a risk factor for incident T2D. METHODS: Two nested case-control studies of cancer allowed calculation of the VAT score based on anthropometric measures and 8 biomarkers among 2,556 participants without T2D. Incident cases were identified from Medicare linkages and self-reports after blood draws in 2001-2006. Cox regression with age as time metric was applied to estimate the association of the VAT score with T2D. RESULTS: During 10.1 ± 2.4 years, 355 incident T2D cases were identified. VAT scores were higher in T2D cases than among those without disease (5.06±0.43 vs. 4.95±0.41; P<0.0001) and significantly associated with T2D (HR = 2.70; 95%CI 1.60, 4.58 per unit) with similar values in men (HR = 2.99; 95%CI 1.03, 8.73) and women (HR = 2.61; 95%CI 1.39, 4.91). A significant association was observed in all five ethnic groups but only statistically significant among Japanese Americans (HR = 6.24; 95%CI 2.34, 16.68). CONCLUSION: These findings support that VAT as estimated by a biomarker-based score predicts T2D incidence beyond BMI in particular among older adults of Japanese ancestry.

Differences in the association of diet quality with body fat distribution between men and women.

BACKGROUND/OBJECTIVE: As dietary intake and endocrine metabolism are vastly different by sex, we evaluated differences in the association of diet quality with body composition between men and women. SUBJECTS/METHODS: Close to 2000 participants from the Multiethnic Cohort completed calibrated quantitative food frequency questionnaires at cohort entry (1993-96) and clinic visit (2013-16), from which the Healthy Eating Index (HEI-2010) was computed. Adiposity measures were obtained through DXA and MRI at clinic visit. Multivariable-adjusted mean adiposity measures were estimated by tertiles of HEI-2010 scores using general linear regression. The associations of diet quality with high visceral fat (VAT) and nonalcoholic fatty liver disease (NAFLD) were examined by logistic regression. To assess sex differences, cross-product terms with the HEI-2010 were added to the models. RESULTS: Mean HEI-2010 scores were higher for women than men at cohort entry (67.4 vs. 64.0) and clinic visit (73.6 vs. 71.0). Past and current diet quality was inversely associated with adiposity measures in men and women. Although interaction terms were not significant, the magnitude of the slopes and differences in adjusted means across tertiles suggested a stronger association for women than men. When comparing individuals who maintained a high vs. poor quality diet over 20 years, women but not men showed significantly lower risks for high VAT, whereas high HEI-2010 scores predicted a lower risk of NAFLD in both sexes. CONCLUSIONS: The inverse association of diet quality with adiposity was similar in both sexes, but diet quality appeared to have a stronger influence on VAT in women than men.

Diet Quality in Midadulthood Predicts Visceral Adiposity and Liver Fatness in Older Ages: The Multiethnic Cohort Study.

OBJECTIVE: The relationship of diet quality assessed by established indices (HEI-2010, AHEI-2010, aMED, DASH) with adiposity measures was examined, especially visceral adipose tissue (VAT) and nonalcoholic fatty liver (NAFL). METHODS: Close to 2,000 participants of the Multiethnic Cohort completed validated food frequency questionnaires at cohort entry (1993-1996) and clinic visit (2013-2016) when they underwent whole-body dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging scans. Linear regression was used to estimate mean values of adiposity measures by dietary index tertiles at baseline and standardized regression coefficients (ßs ) after adjusting for total adiposity and other covariates. Logistic regression of VAT and NAFL on dietary indices was also performed. RESULTS: Higher dietary quality scores at cohort entry were inversely related to all adiposity measures, with the strongest associations for percent liver fat (ßs = -0.14 to -0.08), followed by VAT (ßs = -0.11 to -0.05), BMI (ßs = -0.11 to -0.06), and total body fat (ßs = -0.09 to -0.05). Odds ratios adjusted for total adiposity ranged between 0.57 and 0.77 for NAFL and between 0.41 and 0.65 for high VAT when comparing the highest versus lowest tertiles of diet quality. CONCLUSIONS: These longitudinal findings indicate that maintaining a high-quality diet during mid-to-late adulthood may prevent adverse metabolic consequences related to VAT and NAFL.

Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease: results from the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: We previously reported that 20% of women with chest pain but without obstructive coronary artery disease (CAD) had stress-induced reduction in myocardial phosphocreatine-adenosine triphosphate ratio by phosphorus-31 nuclear magnetic resonance spectroscopy (abnormal MRS), consistent with myocardial ischemia. The prognostic implications of these findings are unknown. METHODS AND RESULTS: Women referred for coronary angiography for suspected myocardial ischemia underwent MRS handgrip stress testing and follow-up evaluation. These included (1) n=60 with no CAD/normal MRS, (2) n=14 with no CAD/abnormal MRS, and (3) n=352 a reference group with CAD. Cardiovascular events were death, myocardial infarction, heart failure, stroke, other vascular events, and hospitalization for unstable angina. Cumulative freedom from events at 3 years was 87%, 57%, and 52% for women with no CAD/normal MRS, no CAD/abnormal MRS, and CAD, respectively (P<0.01). After adjusting for CAD and cardiac risk factors, a phosphocreatine-adenosine triphosphate ratio decrease of 1% increased the risk of a cardiovascular event by 4% (P=0.02). The higher event rate in women with no CAD/abnormal MRS was primarily due to hospitalization for unstable angina, which is associated with repeat catheterization and higher healthcare costs. CONCLUSIONS: Among women without CAD, abnormal MRS consistent with myocardial ischemia predicted cardiovascular outcome, notably higher rates of anginal hospitalization, repeat catheterization, and greater treatment costs. Further evaluation into the underlying pathophysiology and possible treatment options for women with evidence of myocardial ischemia but without CAD is indicated.

Cardiac transplant patients response to the (31)P MRS stress test.

BACKGROUND: Previous studies showed low resting phosphocreatine/adenosine triphosphate (PCr/ATP) ratios within this patient population compared with controls; however, these low PCr/ATP did not correlate with endomyocardial biopsy rejection. One possible explanation is the presence of cardiac allograft vasculopathy (CAV), which might be manifested as a transient ischemic event in the mildly stressed transplanted heart. If transient ischemia is invoked through the (31)P magnetic resonance spectroscopy (MRS) stress test, monitoring of such an event should be achievable and thus implicating possible ischemic involvement. METHODS: Heart transplant patients (n = 25) and normal controls (n = 11) were studied using the (31)P MRS stress test; 10 patients tested positive (> 2 standard deviations [SDs] from control values). Patients also were monitored for heart rate and blood pressure with the handgrip exercise generating a small increase in the rate-pressure product. RESULTS: The percent change (%Delta) in the PCr/ATP ratio in the control group was 1.50% +/- 10.6; the transplant population showed an overall change of -6.7% +/- 18.5. The responders, those that were at or below the 2 SD line from control, had a -25.6 +/- 3.6% Delta PCr/ATP; whereas the non-responders reflect a 5.1 +/- 13.4%. The responders' response is quite striking when considering the threshold for an abnormal PCr/ATP %Delta in response to stress testing was -19.7%, which was the 2 SD mark below the mean value for the reference population. DISCUSSION: The (31)P MRS stress test showed that a possible transient ischemic event occurred in a subset of patients, thus implicating possible CAV in the cardiac transplant patient. Such an approach may provide an early diagnosis of this disease.

Structural growth trajectories and rates of change in the first 3 months of infant brain development.

IMPORTANCE: The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders. OBJECTIVE: To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. DESIGN, SETTING, AND PARTICIPANTS: Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013. MAIN OUTCOMES AND MEASURES: We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms. RESULTS: Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10-13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development. CONCLUSIONS AND RELEVANCE: Normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders.

Susceptibility variants for waist size in relation to abdominal, visceral, and hepatic adiposity in postmenopausal women.

Genome-wide association studies have identified common genetic variants that can contribute specifically to the risk of abdominal adiposity, as measured by waist circumference or waist-to-hip ratio. However, it is unknown whether these genetic risk factors affect relative body fat distribution in the abdominal visceral and subcutaneous compartments. The association between imaging-based abdominal fat mass and waist-size risk variants in the FTO, LEPR, LYPLAL1, MSRA, NRXN3, and TFAP2B genes was investigated. A cross-sectional sample of 60 women was selected among study participants of The Multiethnic Cohort, who were aged 60 to 65 years, of European or Japanese descent, and with a body mass index (calculated as kg/m(2)) between 18.5 and 40. Dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging scans were used to measure adiposity. After adjustments for age, ethnicity, and total fat mass, the FTO variants showed an association with less abdominal subcutaneous fat and a higher visceral-to-subcutaneous abdominal fat ratio, with the variant rs9941349 showing significant associations most consistently (P=0.003 and 0.03, respectively). Similarly, the LEPR rs1137101 variant was associated with less subcutaneous fat (P=0.01) and a greater visceral-to-subcutaneous fat ratio (P=0.03) and percent liver fat (P=0.007). MSRA rs545854 variant carriers had a lower percent of leg fat. Our findings provide initial evidence that some of the genetic risk factors identified for larger waist size might also contribute to disproportionately greater intra-abdominal and liver fat distribution in postmenopausal women. If replicated, these genetic variants can be incorporated with other biomarkers to predict high-risk body fat distribution.

Relationship of intramyocellular lipid to insulin sensitivity may differ with ethnicity in healthy girls and women.

The prevalence of type 2 diabetes is greater among African Americans (AA) vs. European Americans (EA), independent of obesity and lifestyle. We tested the hypothesis that intramyocellular lipid (IMCL) or extramycellular lipid (EMCL) would be associated with insulin sensitivity among healthy young women, and that the associations would differ with ethnic background. We also explored the hypothesis that adipokines and estradiol would be associated with muscle lipid content. Participants were 57 healthy, normoglycemic, women and girls mean age 26 (±10) years; mean BMI 27.3 (±4.8) kg/m²; 32 AA, 25 EA. Soleus IMCL and EMCL were assessed with ¹H magnetic resonance spectroscopy (MRS); insulin sensitivity with an insulin-modified frequently sampled intravenous glucose tolerance test and minimal modeling; body composition with dual-energy X-ray absorptiometry; and intra-abdominal adipose tissue (IAAT) with computed tomography. Adiponectin, leptin, and estradiol were assessed in fasting sera. Analyses indicated that EMCL, but not IMCL, was greater in AA vs. EA (2.55 ± 0.16 vs. 1.98 ± 0.18 arbitrary units, respectively, P < 0.05; adjusted for total body fat). IMCL was associated with insulin sensitivity in EA (r = -0.54, P < 0.05, adjusted for total fat, IAAT, and age), but not AA (r = 0.16, P = 0.424). IMCL was inversely associated with adiponectin (r = -0.31, P < 0.05, adjusted for ethnicity, age, total fat, and IAAT). In conclusion, IMCL was a significant determinant of insulin sensitivity among healthy, young, EA but not AA women. Further research is needed to determine whether the component lipids of IMCL (e.g., diacylglycerol (DAG) or ceramide) are associated with insulin sensitivity in an ethnicity specific manner.

Relationship between Insulin Sensitivity and Muscle Lipids may Differ with Muscle Group and Ethnicity.

Intramyocellular lipid (IMCL) has been inversely associated with insulin sensitivity in some, but not all, studies. This study utilized fast, high-resolution, magnetic resonance spectroscopic imaging (MRSI) to: investigate relationships between muscle lipids (IMCL and extramyocellular lipid (EMCL)) and insulin sensitivity in muscles of varying oxidative capacity, explore ethnic differences in these relationships, and determine whether a eucaloric, low-fat dietary intervention would reduce IMCL and increase insulin sensitivity. Subjects were 30 healthy, African-American (AA; n=14) and European-American (EA; n=16) males, BMI 26.49 (±5.57) kg/m(2), age 21.80 (±7.84) yrs. Soleus and tibialis anterior muscle lipids were quantified using MRSI. Insulin sensitivity was assessed via intravenous glucose tolerance test. A 2-week, eucaloric, low-fat diet intervention was conducted in a sub-group (n=12) subjects with assessments at baseline and post-intervention. Neither IMCL nor EMCL levels differed between ethnicities. In the total group, and within EA (but not AA), both tibialis anterior IMCL and EMCL were inversely associated with insulin sensitivity (P<0.05 for both); soleus muscle lipids were not associated with insulin sensitivity. Soleus, but not tibialis anterior, IMCL declined in both ethnic groups (average 25.3%; p<0.01) following dietary intervention; insulin sensitivity was unchanged. Results suggest that an association of muscle lipids with insulin sensitivity may be influenced by the oxidative capacity of the muscle group studied and may vary with ethnicity.

Elevated brain scyllo-inositol concentrations in patients with Alzheimer's disease.

in vivo (1)H MRS reveals reduced N-acetylaspartate (NAA) and elevated myo-inositol (mI) in patients with mild Alzheimer's disease (AD) and patients with amnestic mild cognitive impairment (MCI). We are unaware of studies that have documented abnormal scyllo-inositol (sI) levels in patients with AD or patients with MCI, although a previous MRS study in older adults has indicated that sI is a peak of interest to measure in AD. Fifteen patients with mild AD, 26 patients with amnestic MCI, and 19 healthy older adults were recruited to this study. All underwent (1)H MRS of the posterior cingulate gyrus of the brain using a 3 T MRI scanner. Increases in the sI/creatine (Cr) ratio were observed in patients with mild AD (P < 0.05). The mI/Cr ratio was raised in patients with mild AD (P < 0.01) and MCI (P < 0.05). Reduced NAA/Cr was detected in patients with mild AD (P < 0.05). The sI/Cr ratio correlated negatively (r = -0.60, P < 0.05) with a measure of clock drawing in patients with mild AD, indicating that impaired cognitive ability in AD is associated with higher concentrations of sI/Cr. In vivo measurement of sI/Cr in the posterior cingulate gyrus of patients with mild AD revealed increases compared with cognitively healthy older adults. Further research on the mechanisms of sI increase in AD is needed. Future studies on the longitudinal course of sI/Cr in MCI and AD appear warranted.

Longitudinal non-invasive proton NMR spectroscopy measurement of vitreous lactate in a rabbit model of ocular hypertension.

To determine whether vitreous lactate concentrations are correlated with intraocular pressure (IOP) rise, retinal ganglion cell (RGC) damage, and nerve fiber layer (NFL) thickness decrease in a rabbit model of ocular hypertension. Also, to learn whether proton nuclear magnetic resonance ((1)H-NMR) spectroscopy can provide sequential, non-invasive in vivo measurements of vitreous lactate. Intra-anterior chamber injections of 20-mum latex beads were used to impede aqueous drainage in New Zealand White rabbits, causing an elevation of IOP. Group I consisted of 12 rabbits in which unilateral elevations in IOP were achieved. Group II consisted of 6 rabbits in which treatment did not cause a change in IOP. The contralateral eye served as a control in both groups. Control eyes received an equal volume injection of vehicle only. IOP was measured for two pre-treatment days and then on post-treatment days 1, 3, 5, 7, 9, 16, 23, 30, and 37. (1)H-NMR spectroscopy was used to measure changes in vitreous lactate concentrations that may be associated with the onset and progression of the pathophysiology. Post-mortem histochemical analysis at the light microscope level was used to quantify changes in the retinal NFL thickness and in the numbers of RGC, and correlate them with IOP and percent change in lactate levels. Baseline IOP in Group I control and treated eyes were 12.0+/-1.9 and 12.5+/-1.3 mmHg, respectively. Between days 5 and 9 post-treatment, the IOP in Group I treated eyes (n=12) rose to 23.9+/-4.2 mmHg. IOP in the control eyes remained unchanged (12.0+/-1.6). Vitreous lactate levels in Group I treated eyes increased by 100%, from pre-treatment values. Levels in control eyes remained unchanged. In Group I, IOP and percent change in lactate concentration in treated eyes were closely correlated throughout the study period (r=0.95; p< or =0.05). Group II control and treated eyes showed no significant changes in either IOP or lactate. Group I treated eyes had a reduced NFL thickness (65+/- 4 microm; n=5) at the temporal medullary ray (MR) compared with control eyes (45+/-6 microm). A smaller reduction was found in the nasal MR areas, where thickness was 53+/-3 microm in treated eyes and 66+/-4 microm in control eyes. RGC numbers also were decreased in the treated eyes (241,222+/-10,920 cells) vs. 322,311+/-8726 cells in control eyes. TdT-mediated dUTP nick-end labeling (TUNEL) indicated that RGC loss in the treated eyes was most likely due to apoptosis. In vivo changes in lactate can be monitored non-invasively over time using (1)H-NMR spectroscopy. Vitreous lactate concentrations increased and returned to baseline concurrently with IOP. The brief elevation in IOP produced a reduction in both the RGC cell numbers and in the thickness of the NFL.

PCr overshoot': a study of the duration in canine myocardium.

The phosphocreatine (PCr) overshoot is a well-documented phenomenon and is readily observable by 31P MRS. In addition, a second 31P MRS observation during ischemia with reperfusion is a diminution in ATP levels. Combining these two as the 'PCr Overshoot' the PCr/ATP ratio may provide an index of viability. However little information is available regarding the duration of this 'overshoot'. For this approach to be useful clinically, the duration of this phenomenon must be ascertained. An open chest canine model of 12 min of ischemia followed by reperfusion (6h) was used. A 2 cm surface coil was sutured to the myocardium and spectra were acquired at 4.7 T. Gated spectra were acquired in <2.5 min with an interpulse delay of 5 s. Integrals of the PCr and ATP (beta) resonances were analyzed using a line-fitting routine. Overall, the PCr signal increased from 22.0+/-0.8 to 25.5+/-0.9 and ATP decreased from 11.7+/-0.4 to 10.0+/-0.4 (arbitrary units). The PCr remained elevated for the entire 6h period and the percentage increase was 15.9%. The ATP remained depleted for the entire 6h period and the percentage decrease was 17.0%. Thus, the clinically relevant and readily observable PCr/ATP is a product of both an increase in PCr and a decrease in ATP for a calculated net increase in PCr/ATP of 39.6%. The PCr/ATP ratio of the ischemia group for baseline, ischemia, 6h reflow, were: 2.33+/-0.18, 1.04+/-0.29 and 3.22+/-0.21. We demonstrate that the 'PCr overshoot' is readily observable and can be monitored noninvasively and nondestructively for 6h. Therefore, the 'PCr overshoot' may be a viable marker of reversible injury in this model and may prove to be applicable for detecting myocardial viability in patients.