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Biomedical subjects

Patrick J Cozzone

Publications and source records attributed to Patrick J Cozzone.

At least 37 records · Page 2Linked to original sources
PubMed2005

Altered functional connectivity related to white matter changes inside the working memory network at the very early stage of MS.

Functional magnetic resonance imaging (fMRI) using paced auditory serial addition test (PASAT) as paradigm was used to study the functional connectivity in 18 patients at the very early stage of multiple sclerosis (MS) compared with 18 controls, to determine the existence of circuitry disturbance inside the working memory network and its relationship with white matter abnormalities assessed by conventional MRI and magnetization transfer ratio (MTR) imaging. The left BA 45/46 was selected as the seed region to compute correlation maps with other brain regions. After obtaining the correlation map for each subject, between-group comparisons were performed using random effect procedure. Compared with controls, patients did not show any greater functional connectivity between left BA 45/46 and other regions during PASAT. In contrast, decrease in functional connectivity was observed in patients between left BA 45/46 and left BA 9, right BA 3, and the anterior cingulate cortex (BA 24). In patients, no correlations were found between altered functional connectivity and clinical data. However, functional connectivity observed between left BA 45/46 and BA 24 in patients was correlated with the MTR of normal appearing white matter, and with brain T(2) lesion load. Altered functional connectivity is present inside the working memory network of patients at the very early stage of MS and is related to the extent of diffuse white matter changes.

Acoustic Stimulation↗
PubMed2005

Noninvasive characterization of myocardial blood flow in diabetic, hypertensive, and diabetic-hypertensive rats using spin-labeling MRI.

OBJECTIVE: Microvascular alterations in the diabetic and hypertensive heart are likely to contribute to heart failure. In this work, myocardial blood flow and left ventricular function were measured in vivo in diabetic, hypertensive, and diabetic-hypertensive rats using MRI methods. METHODS: An 8-week-duration type 1 diabetes was induced by streptozotocin (STZ) in 8 Wistar-Kyoto (WKY) rats (STZ) and in 11 spontaneously hypertensive (SHR) rats (STZ-SHR). Fourteen WKY and 12 SHR served as control and hypertensive groups. Myocardial blood flow quantification was performed using an arterial spin-labeling MRI method. Left ventricular morphology and function were assessed during the same experiment using cine-MRI. RESULTS: Respective myocardial blood flow values for each group were 6.4 +/- 1.1 (WKY), 6.0 +/- 1.9 (STZ), 5.5 +/- 1.3 (SHR), and 4.3 +/- 0.9 mL. g(-1). min(-1) (STZ-SHR). Myocardial blood flow was significantly decreased in STZ-SHR rats compared with the other groups (p <.05, STZ-SHR vs. all groups). Cine-MRI showed morphological alterations in all pathological groups. No alteration of the ejection fraction was observed in the pathological groups. CONCLUSION: Myocardial blood flow is altered in vivo before any sign of heart failure when rats have type 1 diabetes and hypertension simultaneously. When only one of the pathologies occurs, MBF does not vary significantly.

Animals↗
PubMed2005

Metabolic recovery in professional road cyclists: a 31P-MRS study.

PURPOSE: Aerobic training of professional road cyclists is linked to tremendous aerobic capacities that have never been clearly related to what occur in skeletal muscles submitted to a specific exercise. The aim of the present study was to examine specifically metabolic recovery after an incremental cycling exercise performed until exhaustion in professional road cyclists as compared with moderately trained subjects and so using 31P- MRS. METHODS: Subjects performed a progressive cycling exercise on a cycloergometer until exhaustion, then they were positioned back in the magnet (delay lower than 45 s) for recovery scanning. 31P spectra of thigh muscles were time averaged in 2-s blocks at rest and for 15 min throughout the recovery period. RESULTS: For a significantly more intense exercise (477 +/- 28 vs 334 +/- 24 W in controls; P < 0.001), professional road cyclists displayed similar end-of-exercise extrapolated pH values (6.43 +/- 0.16 vs. 6.34 +/- 0.05 in controls) and a significantly higher PCr concentration (20.1 +/- 0.8 vs. 13.3 +/- 0.5 mM in controls, P < 0.001). The pH recovery kinetics provided the evidence of metabolic adaptations related to a specific training in professional cyclists with a significantly faster rate (P < 0.01) of pH return toward basal values (32.8 +/- 18.9 vs 10.8 +/- 6.7 mM x min(-1)). On the contrary, no significant difference was measured for the PCr recovery kinetics. At rest, PDE concentration was significantly higher in professional cyclists (2.50 +/- 0.80 vs 1.76 +/- 0.42 mM), likely indicating a difference regarding fiber-type composition. DISCUSSION: The present data demonstrated for the first time that the tremendous aerobic capacity in professional cyclists is linked to faster pH recovery kinetics after a specific cycling exercise.

Adaptation, Physiological↗
PubMed2005

Defective myocardial blood flow and altered function of the left ventricle in type 2 diabetic rats: a noninvasive in vivo study using perfusion and cine magnetic resonance imaging.

OBJECTIVE: In type 2 diabetes mellitus, cardiovascular complications are related to microvascular abnormalities. In this work, we aimed at characterizing in vivo myocardial blood flow and left ventricular function of the Goto-Kakizaki (GK) rat as a nonobese model of type 2 diabetes. MATERIALS AND METHODS: We performed arterial spin labeling magnetic resonance imaging (MRI) for myocardial blood flow quantification and cine MRI for functional evaluation in free-breathing isoflurane-anesthetized animals. RESULTS: Myocardial blood flow was altered in adult female GK rats compared with age-matched female Wistar rats (4.7 +/- 1.6 vs. 7.1 +/- 1.2 mL/g/min respectively, P = 0.0022). Ejection fraction was decreased in GK compared with Wistar rats (64 +/- 7 vs. 78 +/- 8% respectively, P <0.005), mainly as a result of a loss in left ventricular longitudinal contraction. CONCLUSIONS: Adult female GK rats have defective myocardial blood flow associated with altered left ventricular function. This multiparametric MRI approach in the GK rat is of particular interest for the study of type 2 diabetic cardiomyopathy.

Animals↗
PubMed2004

Heterogeneity of muscle recruitment pattern during pedaling in professional road cyclists: a magnetic resonance imaging and electromyography study.

Although a number of studies have been devoted to the analysis of the activity pattern of the muscles involved in pedaling in sedentary subjects and/or amateur cyclists, data on professional cyclists are scarce and the issue of inter-individual differences has never been addressed in detail. In the present series of experiments, we performed a non-invasive investigation using functional magnetic resonance imaging and surface electromyography to determine the pattern of activity of lower limb muscles during two different exhausting pedaling exercises in eight French professional cyclists. Each subject performed an incremental exercise during which electromyographic activity of eight lower limb muscles and respiratory variables were recorded. After a 3-h recovery period, transverse relaxation times (T2) were measured before and just after a standardized constant-load maximal exercise in order to quantify exercise-related T2 changes. The global EMG activity illustrated by the root mean square clearly showed a large inter-individual difference during the incremental exercise regardless of the investigated muscle (variation coefficient up to 81%). In addition, for most of the muscles investigated, the constant-load exercise induced T2 increases, which varied noticeably among the subjects. This high level of variation in the recruitment of lower limb muscles in professional cyclists during both incremental and constant-load exercises is surprising given the homogeneity related to maximal oxygen consumption and training volume. The high degree of expertise of these professional cyclists was not linked to the production of a common pattern of pedaling and our results provide an additional evidence that the nervous system has multiple ways of accomplishing a given motor task, as has been suggested previously by neural control theorists and experimentalists.

Adult↗
PubMed2004

Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization.

BACKGROUND: Histological anomalies associated with malignant hyperthermia (MH) have been scarcely reported. In some patients susceptible to MH (MHS), central cores have been identified and a genetic association has been proposed, but multiminicore lesions have not been systematically reported. OBJECTIVE: To analyze the association between multiminicores and MHS in a large family with MH with an approach combining histology, in vitro contracture tests, and genetic analysis. PATIENTS AND METHODS: Twenty-nine members of an MH family (147 members) were investigated. MAIN OUTCOME MEASURES: Muscle biopsy specimens were analyzed histologically and with in vitro contracture tests. Genetic analyses were performed to determine the presence of mutations in the ryanodine receptor (RYR1) gene. RESULTS: According to the gold standard in vitro contracture tests, 17 patients were diagnosed as having MHS and 10 as not being susceptible. Multiminicores were found in 16 of the 17 MHS patients and in a single nonsusceptible participant. A linkage between the MH trait and the RYR1 locus in chromosome 19 was demonstrated, whereas no already known mutations were found. Two missense heterozygous mutations (R2676W and T2787S) were identified from sequencing of the entire coding complementary DNA. Overall, we found a significant association between MHS and the presence of multiminicores (chi(2) = 26.5, P<.001) on the one hand and the presence of new mutations in the RYR1 gene (chi(2) = 19.0, P<.001) on the other hand. This remarkably high occurrence of multiminicores in an MHS family is uncommon, and genetic analyses indicate that the association between multiminicores and MHS is linked to a novel R2656W and T2787S substitution present on the same allele of the RYR1 gene. CONCLUSIONS: These results indicate that multiminicore lesions are observed in MHS patients with neither clinical signs related to multiminicore disease nor histological features of congenital myopathies. These multiminicore lesions may be secondary to mutations in the RYR1 gene. As a consequence, these patients must be distinguished from patients with multiminicore disease and from other MHS patients for whom multiminicores are not observed.

DNA Mutational Analysis↗
PubMed2004

Voxel-based analysis of MTR images: a method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis.

PURPOSE: To determine whether voxel-based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS). MATERIALS AND METHODS: We acquired GM MTR maps in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex- and age-matched healthy controls. We evaluated the clinical status of the patients using the MS functional composite score and the expanded disability status scale. A two-sample t-test (P <0.0001, k=20, uncorrected for height threshold) was used to compare GM MTR maps from patients and controls on a voxel-by-voxel basis. We then extracted data from regions with t-values above the statistical threshold to verify the significance of differences using a nonparametric Mann-Whitney U-test. RESULTS: A between-groups comparison of GM maps revealed large abnormalities in the basal ganglia, including the bilateral thalamus, bilateral lenticular nucleus, bilateral head of caudate, and protuberance, and smaller abnormalities in the right insula, right BA 4, and left BA 40. The MTR measured in the left caudate and right insula was inversely correlated with duration following the first clinical event. CONCLUSION: These results suggest that although MS is a multifocal demyelinating disease that affects white matter (WM), a pattern of tissue damage is present inside the GM involving predominantly basal ganglia at the earliest stage of the disease.

Adult↗
PubMed2004

High-resolution myocardial perfusion mapping in small animals in vivo by spin-labeling gradient-echo imaging.

An ECG and respiration-gated spin-labeling gradient-echo imaging technique is proposed for the quantitative and completely noninvasive measurement and mapping of myocardial perfusion in small animals in vivo. In contrast to snapshot FLASH imaging, the spatial resolution of the perfusion maps is not limited by the heart rate. A significant improvement in image quality is achieved by synchronizing the inversion pulse to the respiration movements of the animals, thereby allowing for spontaneous respiration. High-resolution myocardial perfusion maps (in-plane resolution=234 x 468 microm2) demonstrating the quality of the perfusion measurement were obtained at 4.7 T in a group of seven freely breathing Wistar-Kyoto rats under isoflurane anesthesia. The mean perfusion value (group average +/- SD) was 5.5 +/- 0.7 ml g(-1)min(-1). In four animals, myocardial perfusion was mapped and measured under cardiac dobutamine stress. Perfusion increased to 11.1 +/- 1.9 ml g(-1)min(-1). The proposed method is particularly useful for the study of small rodents at high fields.

Animals↗
PubMed2003

Early changes in glucose and phospholipid metabolism following apoptosis induction by IFN-gamma/TNF-alpha in HT-29 cells.

The effects of apoptosis induction on glucose and phospholipid metabolite levels in cancer were studied using human colon adenocarcinoma cells (HT-29). Apoptosis was induced by co-incubation with 200 U/ml tumor necrosis factor (TNF)-alpha for 4, 8 or 15 h, after sensitization with 500 U/ml interferon (IFN)-gamma for 7 h. Perchloric acid extracts were analyzed by (1)H and (31)P nuclear magnetic resonance (NMR) spectroscopy. Significantly increased lactate and NTP (all nucleoside 5'-triphosphates) signals were detected 4 h after apoptosis-inducing IFN-gamma/TNF-alpha treatment, but not in cells which were TNF-alpha-treated without IFN-gamma preincubation. Simultaneous lactate and NTP changes, if confirmed in vivo, may serve as early, non-invasive markers of treatment response in some tumors.

Apoptosis↗
PubMed2003

ATP synthesis and proton handling in muscle during short periods of exercise and subsequent recovery.

We used (31)P-magnetic resonance spectroscopy to study proton buffering in finger flexor muscles of eight healthy men (25-45 yr), during brief (18-s) voluntary finger flexion exercise (0.67-Hz contraction at 10% maximum voluntary contraction; 50/50 duty cycle) and 180-s recovery. Phosphocreatine (PCr) concentration fell 19 +/- 2% during exercise and then recovered with half time = 0.24 +/- 0.01 min. Cell pH rose by 0.058 +/- 0.003 units during exercise as a result of H(+) consumption by PCr splitting, which (assuming no lactate production or H(+) efflux) implies a plausible non-P(i) buffer capacity of 20 +/- 3 mmol. l intracellular water(-1). pH unit(-1). There was thus no evidence of significant glycogenolysis to lactate during exercise. Analysis of PCr kinetics as a classic linear response suggests that oxidative ATP synthesis reached 48 +/- 2% of ATP demand by the end of exercise; the rest was met by PCr splitting. Postexercise pH recovery was faster than predicted, suggesting "excess proton" production, with a peak value of 0.6 +/- 0.2 mmol/l intracellular water at 0.45 min of recovery, which might be due to, e.g., proton influx driven by cellular alkalinization, or a small glycolytic contribution to PCr resynthesis in recovery.

Adenosine Triphosphate↗
PubMed2003

Non-invasive investigations of muscular fatigue: metabolic and electromyographic components.

Muscle fatigue, which is defined as the decline in muscle performance during exercise, may occur at different sites along the pathway from the central nervous system through to the intramuscular contractile machinery. Historically, both impairment of neuromuscular transmission and peripheral alterations within the muscle have been proposed to be involved in the development of fatigue. However, according to the more recent studies, muscle energetics would have a key role in this process. Intramyoplasmic accumulation of inorganic phosphate (P(i)) and limitation in ATP availability are frequently proposed as the causative factors of fatigue development. Although attractive, these hypotheses have been elaborated on the basis of experimental results obtained in vitro and their physiological relevance has never been clearly demonstrated in vivo. In that context, non-invasive methods such as 31-phosphorus magnetic resonance spectroscopy ((31)P MRS) and electromyographic (EMG) recordings have been employed to understand both metabolic and electrical aspects of muscle fatigue under physiological condition. The main results of these studies are reviewed in the present paper.

Animals↗
PubMed2003

NOS substrate during cardioplegic arrest and cold storage decreases stunning after heart transplantation in a rat model.

BACKGROUND: In this study, we evaluated how adding L-arginine to Centre de Résonance Magnétique Biologique et Médicale (CRMBM) solution affected myocardial performance during post-ischemic in vivo reperfusion. METHODS: Experiments were conducted using a modified Lewis-Lewis heterotopic heart transplantation model, with a total ischemic time of 3 hours followed by 1 or 24 hours of blood reperfusion. Heart grafts were arrested using intra-aortic injection of CRMBM solution, either supplemented or not supplemented with 2 mmol/liter L-arginine (n = 12 in each group). We measured systolic indexes and simultaneously performed phosphorus magnetic resonance spectroscopy ((31)P MRS). We quantified total endothelial nitric oxide synthase (eNOS) protein using the Western blot test of freeze-clamped hearts. RESULTS: Contractility during early reperfusion was significantly better in grafts arrested with CRMBM solution enriched with L-arginine: mean rate pressure product, 11249 +/- 1548 vs 5637 +/- 1118 mm Hg/min (p = 0.05), and maximal first derivative of the pressure signal (dP/dt(max)), 1721 +/- 177 vs 1214 +/- 321 mm Hg/sec (p = 0.013). Conversely, during late reperfusion, contractility did not relate to the nature of the preservation solution. The presence of L-arginine in the CRMBM solution did not alter time-related variations of high-energy phosphate ratios measured using in vivo (31)P MRS. The eNOS protein level decreased significantly during early compared with late reperfusion, with no effect caused by L-arginine. CONCLUSIONS: During early reperfusion, the limited myocardial stunning observed with CRMBM solution containing L-arginine does not relate to energy metabolism but to better preservation of the NO pathway.

Allopurinol↗
PubMed2003

Use of proton magnetic resonance spectroscopy of the brain to differentiate gliomatosis cerebri from low-grade glioma.

OBJECT: Gliomatosis cerebri (GC), a rare entity characterized by a widespread infiltration of brain by tumor, lacks objective and quantitative diagnostic criteria. Single-voxel spectroscopy and chemical shift imaging (two-dimensional proton magnetic resonance [MR] spectroscopy) were performed using both short (20- or 22-msec) and long (135-msec) echo times in nine patients suffering from GC, nine patients with low-grade gliomas (LGGs), and 25 healthy volunteers to establish the precise metabolic pattern of this uncommon brain neoplasm. METHODS: The gliomatosis infiltration was characterized by markedly elevated levels of creatine-phosphocreatine (Cr) and mvo-inositol (Ins), a reduced level of N-acetyl aspartate (NAA), and a moderately elevated level of choline-containing compounds (Cho). This pattern differs strikingly from LGGs, which are characterized by elevated levels of Cho and Ins, markedly reduced levels of NAA, and low-to-normal Cr concentrations. Although the distinction between GC and LGG, based on histological and MR imaging criteria, is a matter of debate, MR spectroscopy produces valuable information for the differentiation between these two entities and, hence, the choice of therapeutic strategy. It also provides new insight into the pathophysiology of GC because elevated Cr and Ins levels may be related to proliferation of glial elements or, more probably, activation of normal glia. Elevated levels of Cho reflect cellular proliferation and reduced NAA corresponds to reversible neuronal injury and/or focal invasion by the tumor process. CONCLUSIONS: Owing to the unfavorable clinical outcome associated with GC compared with that associated with LGG, the findings of this study illustrate the diagnostic and prognostic value of proton MR spectroscopy in the characterization of infiltrating gliomas.

Adolescent↗
PubMed2002

Objective and noninvasive metabolic characterization of donor hearts by phosphorous-31 magnetic resonance spectroscopy.

OBJECTIVE: The authors performed a multi-institutional, prospective, blind study on hearts from local donors to validate the feasibility and accuracy of the metabolic evaluation of human hearts by phosphorus-31 ( P) magnetic resonance spectroscopy (MRS) before transplantation. METHODS: Twenty-one hearts were separated into two groups according to a transplantation score (TS) on the basis of the current clinical and echocardiographic evaluation as follows: TS1 (n=7), grafts for United Network for Organ Sharing (UNOS) 1 patients only; and TS2 (n=14), grafts suitable for UNOS 2 patients. All hearts were cold preserved with Celsior and underwent ex situ P MRS to measure ratios of various high-energy phosphate metabolites and the intracellular pH (pHi). RESULTS: The total duration of the MRS procedure was 32 min, thereby not unacceptably increasing the total ischemic time for the transplanted grafts. Phosphocreatine (PCr) and inorganic phosphate (Pi ) was significantly different between the two groups (0.95+/-0.29 for TS1 and 2.05+/-0.74 for TS2). The difference in pHi was also significant (7.44+/-0.13 for TS1 and 7.64+/-0.19 for TS2). CONCLUSIONS: Determination of PCr-Pi and pHi as markers of ischemic injury before transplantation can be considered as an objective and accurate criterion for the decision to accept or refuse heart grafts for transplantation.

Adult↗
PubMed2002

New parameters reducing the interindividual variability of metabolic changes during muscle contraction in humans. A (31)P MRS study with physiological and clinical implications.

Interindividual variations in skeletal muscle metabolism make comparative analyses difficult. In this study, we have addressed the issue of capturing the variability of metabolic performance observed during muscle exercise in humans by using an original method of normalization.Metabolic changes induced by various kinds of exercise were investigated using 31P magnetic resonance spectroscopy (MRS) at 4.7 T in 65 normal subjects (23 women and 42 men) and 12 patients with biopsy-proven muscular disorders. Large variations in the extent of PCr breakdown and intracellular acidosis were recorded among subjects and exercise protocols. For all the data pooled, the amplitude of mechanical performance accounts for 50% of these variations. When scaled to the work output, variations of PCr consumption account for 65% of pH changes through a linear relationship. This linear relationship was substantially improved (90%) when both variables were scaled to the square of work output performed (P1 and P2). By capturing most of the initial interindividual variability (90%), P1 vs. P2 relationship represents an ideal standardization procedure, independent of any anthropometric measurements. This relationship also discloses a significant link between the extent of PCr breakdown and intracellular acidosis regardless of exercise protocol. Moreover, changes in the slope of the P1 vs. P2 regression curve, as measured in old subjects and in selected patients, directly reflect alterations of energy production in muscle.

Adult↗
PubMed2002

Metabolic underpinnings of the paradoxical net phosphocreatine resynthesis in contracting rat gastrocnemius muscle.

Net phosphocreatine (PCr) resynthesis during muscle contraction is a paradoxical phenomenon because it occurs under conditions of high energy demand. The metabolic underpinnings of this phenomenon were analyzed non-invasively using 31P-magnetic resonance spectroscopy in rat gastrocnemius muscle (n=11) electrically stimulated (7.6 Hz, 6 min duration) in situ under ischemic and normoxic conditions. During ischemic stimulation, [PCr] initially fell to a steady state (9+/-5% of resting concentration) which was maintained for the last 5 min of stimulation, whereas isometric force production decreased to a non-measurable level beyond 3 min. Throughout normoxic stimulation, [PCr] and force production declined to a steady state after respectively 1 min (5+/-3% of resting concentration) and 3.25 min (21+/-8% of initial value) of stimulation. Contrary to the observations under ischemia, a paradoxical net PCr resynthesis was recorded during the last 2 min of normoxic stimulation and was not accompanied by any improvement in force production. These results demonstrate that the paradoxical net PCr resynthesis recorded in contracting muscle relies exclusively on oxidative energy production and could occur in inactivated fibers, similarly to PCr resynthesis during post-exercise recovery.

Adenosine Triphosphate↗