Decreased Hippocampal Metabolism in Amnestic Mild Cognitive Impairment: Positron Emission Tomography Study

Objective@#Little is known about factors influencing of hippocampal metabolism (HM) in mild cognitive impairment (MCI). Our objective was to determine whether HM in patients with amnestic MCI (aMCI) is decreased than non-amnestic MCI (naMCI). @*Methods@#Overall, 32 MCI patients underwent 18F-fluorodeoxyglucose-positron emission tomography. They were characterized as aMCI (n=18) or naMCI (n=14) according to comprehensive neuropsychological criteria. Analysis of variances were used to assess differences on HM between aMCI and naMCI after controlling age, sex, education and Korean version of Mini Mental Status Examination. @*Results@#We found that HM was more decreased in aMCI than naMCI. This result was not changed after controlling hippocampal volume. @*Conclusion@#Our findings suggest that aMCI is associated with decreased HM in MCI.

Effect of Amyloid Deposition in PET on Hippocampal Metabolism in Amnestic-Mild Cognitive Impairment : Pilot Study / 생물치료정신의학

OBJECTIVES: Most studies of hippocampal metabolism(HM) in amnestic mild cognitive impairment(aMCI) gave inconsistent results. Our objective was to evaluate the effect of amyloid-beta(Aβ) status on hippocampal metabolism in aMCI.METHODS: Overall, 23 aMCI underwent three-dimensional magnetic resonance imaging(MRI), ¹⁸F-fluorodeoxyglucose-positron emission tomography(¹⁸FDG-PET) and ¹⁸F-Fluorbetaben amyloid positron emission tomography (amyloid-PET). According to Aβ status on amyloid PET, 23 aMCI were classified as either Aβ+aMCI(N=13) or Aβ−aMCI(N=10). The primary outcome was HM using ¹⁸FDG-PET and we investigate the difference on HM between Aβ+aMCI and Aβ−aMCI using analysis of variance(ANOVA) model, after controlling hippocampal volume.RESULTS: We found that HM was more decreased in Aβ+aMCI than Aβ−aMCI. This result was not changed after controlling hippocampal volume.CONCLUSION: Our findings suggest that Aβ+ is associated with decreased HM, regardless of hippocampal volume, in aMCI.

Altered Cortical Thicknesses of Left Pars Opercularis and Left Lateral Occipital Gyrus Can Be Associated with Psychotic Symptoms in Patients with Alzheimer's Disease

OBJECTIVE: The aims of this study was to present an association between the presence of psychotic symptoms and cortical thicknesses/subcortical volumes in patients with Alzheimer's disease (AD). METHODS: Fourteen AD patients with psychotic symptoms and 41 without psychotic symptoms underwent 3T MRI scanning. After adjusting the effects of confounding variables, the cortical thicknesses were compared between the AD patients with and without psychotic symptoms in multiple regions, across the continuous cortical surface. In addition, the subcortical volumes were compared with a structure-by-structure manner. RESULTS: AD patients with psychotic symptoms were characterized by significant smaller cortical thickness of left pars opercularis (F=4.67, p=0.02) and left lateral occipital gyrus (F=6.05, p=0.04) rather than those without psychotic symptoms, after adjusting the effects of age and scores on the Stroop test, non-psychotic items of Neuropsychiatry Inventory and Clinical Dementia Rating, triglyceride level and total intracranial volume. However, there were no significant differences in the subcortical volume between the two groups. CONCLUSION: These results suggest that AD psychosis may reflect more severe deterioration of neuropathologic change in specific brain region.

Distinguishing Tendon and Ligament Fibroblasts Based on ¹H Nuclear Magnetic Resonance Spectroscopy

Tendon and ligament (T/L) have been known to be obviously different from each other in tissue level. However, due to the overlapping gene markers, distinction in cellular level has not been clearly verified yet. Recently, the use of nuclear magnetic resonance (NMR) spectroscopy has shown the potential to detect biological markers in cellular level. Therefore, in this study we applied a non-invasive technique based on NMR spectroscopy to establish biomarkers to distinguish between T/L fibroblasts. In addition the cellular morphologies and gene expression patterns were also investigated for comparison through optical microscopy and real-time polymerase chain reaction (PCR). No difference was observed from morphology and real-time PCR results, either as expected. However, we found clear differences in their metabolomic spectra using ¹H NMR spectroscopy. The calculated integral values of fatty acids (with chemical shifts at ~0.9, 1.26, 1.59, 2.05, 2.25, and 2.81 ppm), lactate (~1.33 ppm), and leucine (~2.72 ppm) were significantly different between the two types of fibroblasts. To be specific tendon group exhibited higher level of the metabolite than ligament group. In conclusion, in-cell metabolomic evaluation by NMR technique used in this study is believed to provide a promising tool in distinguishing cell types, especially T/L cells, which cannot be classified by conventional biological assays.

Impact of Metabolic Syndrome on the White Matter Integrity in Alzheimer's Disease Patients : Tract-Based Spatial Statistics Study under 3-Tesla MRI

OBJECTIVE: The aim of this study is to determine whether there is any difference in white matter (WM) integrity between Alzheimer's disease (AD) with metabolic syndrome (MetS) and without MetS. METHODS: Altogether, 30 subjects were finally recruited from the Memory Impairment Clinics of Pusan National University Hospital in Korea. All subjects (AD with MetS : n=15, matched AD without MetS for age, gender and year of education : n=15) were underwent 3-tesla magnetic resonance imaging scans of diffusion tensor imaging. RESULTS: The mean fractional anisotropy of the AD with MetS was lower (p<0.05) in right posterior corona radiate, right corticospinal tract and right superior longitudinal fasciculus than that of the AD without MetS. CONCLUSION: Our findings suggest that WM integrity damage.

The Correlation of Levels of Serum Lipid, Homocysteine, and Folate with Volumes of Hippocampus, Amygdala, Corpus Callosum, and Thickness of Entorhinal Cortex in Patients with Amnestic Mild Cognitive Impairment or Dementia of Alzheimer's Type

OBJECTIVES: In this study, the authors evaluated the correlation between levels of serum lipid, homocysteine, and folate with volumes of hippocampus, amygdala, corpus callosum, and in patients with amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD) type. METHODS: The study recruited patients who visited the dementia clinic of Haeundae Paik Hospital in Korea between March 2010 and June 2014. Among those, patients who had taken the neurocognitive test, brain magnetic resonance imaing, tests for serum lipid, homocysteine, folate, and apolipoprotein E (APOE) genotyping and diagnosed with aMCI or AD were included for analysis. Bilateral hippocampus, entorhinal cortex, amygdala and corpus callosum were selected for region of interest (ROI). The cross-sectional relationships between serum lipid, homocysteine, folate and ROI were assessed by partial correlation analysis and multiple linear regression analysis. RESULTS: In patients with aMCI, old age (> 80) and APOE epsilon4 carrier were associated with AD [odds ration (OR) : 12.80 ; 95% confidence interval (CI) : 2.25-72.98 and OR : 4.48 ; 95% CI : 1.58-12.67, respectively]. In patients with aMCI or AD, volumes and thickness of ROI were inversely correlated with levels of serum lipid and homocysteine. In multiple linear regression analyses, higher total cholesterol level was related to lower left, right hippocampus volume and left amygdala volume ; higher low-density lipoprotein cholesterol was related to lower right entorhinal cortex thickness ; higher homocysteine level was related to lower corpus callosum volume. CONCLUSIONS: Higher serum lipid and homocysteine levels are associated with decreased volume of hippocampus, amygdala, corpus callosum and entorhinal cortex thickness in patients with aMCI or AD. These findings suggest that serum lipid and homocysteine levels are associated with AD as a modifiable risk factor.

Automated Classification to Predict the Progression of Alzheimer's Disease Using Whole-Brain Volumetry and DTI

OBJECTIVE: This study proposes an automated diagnostic method to classify patients with Alzheimer's disease (AD) of degenerative etiology using magnetic resonance imaging (MRI) markers. METHODS: Twenty-seven patients with subjective memory impairment (SMI), 18 patients with mild cognitive impairment (MCI), and 27 patients with AD participated. MRI protocols included three dimensional brain structural imaging and diffusion tensor imaging to assess the cortical thickness, subcortical volume and white matter integrity. Recursive feature elimination based on support vector machine (SVM) was conducted to determine the most relevant features for classifying abnormal regions and imaging parameters, and then a factor analysis for the top-ranked factors was performed. Subjects were classified using nonlinear SVM. RESULTS: Medial temporal regions in AD patients were dominantly detected with cortical thinning and volume atrophy compared with SMI and MCI patients. Damage to white matter integrity was also accredited with decreased fractional anisotropy and increased mean diffusivity (MD) across the three groups. The microscopic damage in the subcortical gray matter was reflected in increased MD. Classification accuracy between pairs of groups (SMI vs. MCI, MCI vs. AD, SMI vs. AD) and among all three groups were 84.4% (+/-13.8), 86.9% (+/-10.5), 96.3% (+/-4.6), and 70.5% (+/-11.5), respectively. CONCLUSION: This proposed method may be a potential tool to diagnose AD pathology with the current clinical criteria.

Comparison of the Medication Effects between Milnacipran and Pregabalin in Fibromyalgia Syndrome Using a Functional MRI: a Follow-up Study

PURPOSE: In this study, the medication effects of Milnacipran and Pregabalin, as well known as fibromyalgia treatment medicine, in fibromyalgia syndrome patients were compared through the change of BOLD signal in pain related functional MRI. MATERIALS AND METHODS: Twenty fibromyalgia syndrome patients were enrolled in this study and they were separated into two groups according to the treatment medicine: 10 Milnacipran (MLN) treatment group and 7 Pregabalin (PGB) treatment group. For accurate diagnosis, all patients underwent several clinical tests. Pre-treated and post-treated fMRI image with block-designed pressure-pain stimulation for each group were obtained to conduct the statistical analysis of paired t-test and two sample t-test. All statistical significant level was less than 0.05. RESULTS: In clinical tests, the clinical scores of the two groups were not significantly different at pre-treatment stage. But, PGB treatment group had lower Widespread Pain Index (WPI) and Brief Fatigue Inventory (BFI) score than those of MLN treatment group at post-treatment stage. In functional image analysis, BOLD signal of PGB treatment group was higher BOLD signal at several regions including anterior cingulate and insula than MLN treatment group at post-treatment stage. Also, paired t-test values of the BOLD signal in MLN group decreased in several regions including insula and thalamus as known as 'pain network'. In contrast, size and number of regions in which the BOLD signal decreased in PGB treatment group were smaller than those of MLN treatment group. CONCLUSION: This study showed that MLN group and PGB group have different medication effects. It is not surprising that MLN and PGB have not the same therapeutic effects since these two drugs have different medicinal mechanisms such as antidepressants and anti-seizure medication, respectively, and different detailed target of fibromyalgia syndrome treatment. Therefore, it is difficult to say which medicine will work better in this study.

Reproducibility Analysis of Brain Volumetry Measured from Inter MR Scanner of Multi-Institute

PURPOSE: The aim of this study was to evaluate the variations of brain volumetry between the different MR scanners or the different institutes. MATERIALS AND METHODS: Ten normal subjects were scanned at four different MR scanners, two of them were the same models, to measure inter-MR scanner variations using intraclass correlation coefficient (ICC), coefficient of variation (CV) and percent volume difference (PVD) and to calculate minimal thresholds to detect the significant volumetric changes in gray matter and subcortical regions. RESULTS: Averaged statistical reliability (ICC = 0.837) and volumetric variation (CV = 4.310%) in all segmented regions were observed on overall MR scanners. Comparing the segmented volumes with PVD between two MR scanners, volumetric differences on same models were the lowest (PVD = 3.611%) and volume thresholds were calculated with 7.168%. PVD results and thresholds values on systemically different MR scanners were evaluated with 5.785% and 11.340% respectively. CONCLUSION: Authors conclude that the reliability of brain volumetry is not so high. Calibration studies of MRI system and image processing are essential to reduce the volumetric variability. Additionally, frameworks comprised of database and algorithms with high-speed image processing are also required for the efficient image data management.

A Comparison Study on Human Brain Volume of White Matter, Gray Matter and Hippocampus Depending on Magnetic Resonance Imaging Conditions and Applied Brain Template

PURPOSE: The aim of this study was to examine the volume differences of human brain 3-D MR images obtained by automatic segmentation methods depending on brain templates and image acquisition conditions, respectively. MATERIALS AND METHODS: 3D T1-weighted MR images oriented in coronal and sagittal plane were acquired from eight healthy subjects (29.5+/-5.66 years) using two identical 3T MR scanners at different sites. Caucasian brain template and Korean elderly brain template were applied for the same subject to segment brain structural region. Volumetric differences and variation of gray matter, white matter and hippocampus depending on scan orientations and brain template types were statistically evaluated. RESULTS: Volumetric measurements have some different results for the same subject images depending on scan orientation in identical MR scanners but not significantly. However, all segmented volumes relied upon brain templates were significantly different (p<0.05). Small variation of the volume in gray matter, white matter (coefficient of variation, CV< or =1%) and hippocampus (CV< or =3%) were obtained. Comparing the mean CV in all segmented regions, variation of scan orientation was not significantly different with inter scanner variation but variation relied upon brain templates were significantly different (p<0.001). CONCLUSION: Authors found that brain template regarding the specific properties of the subjects is required to reduce the errors of brain volumetry.

Time Resolution Improvement of MRI Temperature Monitoring Using Keyhole Method

PURPOSE: This study proposes the keyhole method in order to improve the time resolution of the proton resonance frequency(PRF) MR temperature monitoring technique. The values of Root Mean Square (RMS) error of measured temperature value and Signal-to-Noise Ratio(SNR) obtained from the keyhole and full phase encoded temperature images were compared. MATERIALS AND METHODS: The PRF method combined with GRE sequence was used to get MR temperature images using a clinical 1.5T MR scanner. It was conducted on the tissue-mimic 2% agarose gel phantom and swine's hock tissue. A MR compatible coaxial slot antenna driven by microwave power generator at 2.45GHz was used to heat the object in the magnetic bore for 5 minutes followed by a sequential acquisition of MR raw data during 10 minutes of cooling period. The acquired raw data were transferred to PC after then the keyhole images were reconstructed by taking the central part of K-space data with 128, 64, 32 and 16 phase encoding lines while the remaining peripheral parts were taken from the 1st reference raw data. The RMS errors were compared with the 256 full encoded self-reference temperature image while the SNR values were compared with the zero filling images. RESULTS: As phase encoding number at the center part on the keyhole temperature images decreased to 128, 64, 32 and 16, the RMS errors of the measured temperature increased to 0.538, 0.712, 0.768 and 0.845degrees C, meanwhile SNR values were maintained as the phase encoding number of keyhole part is reduced. CONCLUSION: This study shows that the keyhole technique is successfully applied to temperature monitoring procedure to increases the temporal resolution by standardizing the matrix size, thus maintained the SNR values. In future, it is expected to implement the MR real time thermal imaging using keyhole method which is able to reduce the scan time with minimal thermal variations.

Preliminary Study on the MR Temperature Mapping using Center Array-Sequencing Phase Unwrapping Algorithm

PURPOSE: To investigate the feasibility and accuracy of Proton Resonance Frequency (PRF) shift based magnetic resonance (MR) temperature mapping utilizing the selfdeveloped center array-sequencing phase unwrapping (PU) method for non-invasive temperature monitoring. MATERIALS AND METHODS: The computer simulation was done on the PU algorithm for performance evaluation before further application to MR thermometry. The MR experiments were conducted in two approaches namely PU experiment, and temperature mapping experiment based on the PU technique with all the image postprocessing implemented in MATLAB. A 1.5T MR scanner employing a knee coil with T2* GRE (Gradient Recalled Echo) pulse sequence were used throughout the experiments. Various subjects such as water phantom, orange, and agarose gel phantom were used for the assessment of the self-developed PU algorithm. The MR temperature mapping experiment was initially attempted on the agarose gel phantom only with the application of a custom-made thermoregulating water pump as the heating source. Heat was generated to the phantom via hot water circulation whilst temperature variation was observed with T-type thermocouple. The PU program was implemented on the reconstructed wrapped phase images prior to map the temperature distribution of subjects. As the temperature change is directly proportional to the phase difference map, the absolute temperature could be estimated from the summation of the computed temperature difference with the measured ambient temperature of subjects. RESULTS: The PU technique successfully recovered and removed the phase wrapping artifacts on MR phase images with various subjects by producing a smooth and continuous phase map thus producing a more reliable temperature map. CONCLUSION: This work presented a rapid, and robust self-developed center arraysequencing PU algorithm feasible for the application of MR temperature mapping according to the PRF phase shift property.

Ex Vivo 1H MR Spectroscopy: Normal gastric and cancer tissue

PURPOSE: In this study, we attempted to ascertain the proton magnetic resonance spectroscopy (1H MRS) peak characteristics of human gastric tissue layers and finally to use the metabolic peaks of MRS to distinguish between normal and abnormal gastric specimens. MATENRIALS AND METHODS: Ex-vivo 1H MRS examinations of thirty-five gastric specimens were performed to distinguish abnormal gastric tissues invaded by carcinoma cells from normal stomach-wall tissues. High-resolution 400-MHz (9.4-T) 1H nuclear magnetic resonance (NMR) spectra of two gastric layers, a proper muscle layer, and a composite mucosa- submucosa layer were compared with those of clinical 64- MHz (1.5-T) MR spectra. Three-dimensional spoiled gradient recalled (SPGR) images were used to determine the size and the position of a voxel for MRS data collection. RESULTS: For normal gastric tissue layers, the metabolite peaks of 400-MHz 1H MRS were primarily found to be as follows: lipids at 0.9 ppm and 1.3 ppm; alanine at 1.58 ppm; N-acetyl neuraminic acid (sialic acid) at 2.03 ppm; and glutathione at 2.25 ppm in common. The broad and feature-less spectral peaks of the 64-MHz MRS were bunched near 0.9, 1.3, and 2.0, and 2.2 ppm in human specimens without respect to layers. In a specimen (Borrmmann type III) with a tubular adenocarcinoma, the resonance peaks were measured at 1.26, 1.36 and 3.22 ppm. All the peak intensities of the spectrum of the normal gastric tissue were reduced, but for gastric tumor tissue layers, the lactate peak split into 1.26 and 1.39 ppm, and the peak intensity of choline at 3.21 ppm was increased. CONCLUSION: We found that decreasing lipids, an increasing lactate peak that split into two peaks, 1.26 ppm and 1.36 ppm, and an increasing choline peak at 3.22 ppm were markers of tumor invasion into the gastric tissue layers. This study implies that MR spectroscopy can be a useful diagnostic tool for gastric cancer.

Ex Vivo 1H MR Spectroscopy: Normal gastric and cancer tissue

PURPOSE: In this study, we attempted to ascertain the proton magnetic resonance spectroscopy (1H MRS) peak characteristics of human gastric tissue layers and finally to use the metabolic peaks of MRS to distinguish between normal and abnormal gastric specimens. MATENRIALS AND METHODS: Ex-vivo 1H MRS examinations of thirty-five gastric specimens were performed to distinguish abnormal gastric tissues invaded by carcinoma cells from normal stomach-wall tissues. High-resolution 400-MHz (9.4-T) 1H nuclear magnetic resonance (NMR) spectra of two gastric layers, a proper muscle layer, and a composite mucosa- submucosa layer were compared with those of clinical 64- MHz (1.5-T) MR spectra. Three-dimensional spoiled gradient recalled (SPGR) images were used to determine the size and the position of a voxel for MRS data collection. RESULTS: For normal gastric tissue layers, the metabolite peaks of 400-MHz 1H MRS were primarily found to be as follows: lipids at 0.9 ppm and 1.3 ppm; alanine at 1.58 ppm; N-acetyl neuraminic acid (sialic acid) at 2.03 ppm; and glutathione at 2.25 ppm in common. The broad and feature-less spectral peaks of the 64-MHz MRS were bunched near 0.9, 1.3, and 2.0, and 2.2 ppm in human specimens without respect to layers. In a specimen (Borrmmann type III) with a tubular adenocarcinoma, the resonance peaks were measured at 1.26, 1.36 and 3.22 ppm. All the peak intensities of the spectrum of the normal gastric tissue were reduced, but for gastric tumor tissue layers, the lactate peak split into 1.26 and 1.39 ppm, and the peak intensity of choline at 3.21 ppm was increased. CONCLUSION: We found that decreasing lipids, an increasing lactate peak that split into two peaks, 1.26 ppm and 1.36 ppm, and an increasing choline peak at 3.22 ppm were markers of tumor invasion into the gastric tissue layers. This study implies that MR spectroscopy can be a useful diagnostic tool for gastric cancer.

Localized Single Voxel 1H MR Spectroscopy Toward Routine Clinical Use

PURPOSE: To evaluate the utomated 1H magnetic resonance spectroscopy (1H-MRS) method for a routine clinical use, various regions of the normal human brain were examined for regional variations, the reproducibility, and thequality control of the spectral data. MATERIALS AND METHODS: Localized 1H-MRS was performed in a GE 1.5T SIGNAMRI/MRS system using the automated method(PROton brain Exam : PROBE). Six regions of the human brain from normal volunteers (N=25, age=23-65) were examined : Occipital gray matter, parietal white matter, frontal white matter, pons, cerebellum, and basal ganglia regions. STEAM was used as the localization method with the following parameters : TE=30 msec, TR=3.0 sec, AVG=48 AVG, NEX=2, Spectral Width (SW)=2500 Hz, Size (SI)=2048 points (2K),and the size of voxel=7-9 ml, The reproducibility and the quality control of the spectral date were evaluated. RESULTS: For the 6 regions, the regional variation by the spectral patterns and the metabolites ratios relative to creatine was well demonstrated. Rates of the auto prescan success and the percentages of obtaining the acceptable quality spectra were high in the parietal white matter, occipital gray matter, and basal gangliaregions, and low in the frontal white matter and pons regions. CONCLUSION: PROBE is a highly practical as well asreliable method to produce reproducible quality spectra that represent the regional metabolic variations in the human brain, PROBE can be used as a single spectroscopic exam or as an additional series to a routine brain MRI exam, which takes less than 10 minutes for acquiaition of one spectrum. In order to obtain good quality spectra, agood quality control scheme of the MR instrument is mandatory.

Comparison of Gadolinium Polylysine and Gadopentetate in Contrast Enhanced MR Imaging of IVlyocardial Ischemia-Reperfusion in Cats

PURPOSE: To assess the signal enhancement by gadolinium-DTPA-polylysine (Gd-polylysine) as compared to gadopentetate (Gd-DTPA) in MR imaging of heart that have undergone ischemia-reperfusion, and to estimate the extent of myocardial damage covered bythe MR signal enhancement. MATERIALS AND METHODS: A series of contrast enhanced cardiac MR images were obtained from 17 cats subjected to a 90 minutes of occlusion of the left anterior descending coronary artery (LAD) followed by a 90 minutes of raperfusion. Time courses of changes in the signal intensity (Sl) of the ischemic area were measu red in Gd-polylysine group (8 cats) and Gd- DTPA group (9 cats). The size of U R signal enhanced area was then compared to the sizes of infarction and the area at risk revealed byTTC histochemical staining. RESULTS: Maximum Sis were obtained at 60 minutes and 30 minutes after injection of the contrast material, respectively for Gd-polylysine group and Gd-DTPA group. Signal enhancement was stronger and persistent for a longer period in Gd-polylysine group than in GD-DTPA group. Sizes of the enhanced area, the infarction, and the area at risk were about 30%, 15%, and 50% of the total left ventricle (LV) area; the difference between the groups was statistically insignificant. CONCLUSION: Gd-polylysine can be used better for a blood pool marker than Gd-DTPA in MR imaging of myocardial ischemia, due to its strong and persistent signal enhancement. The MR signal enhanced area includes both the infarcted area and a portion of the area at risk.

Protective Effect of Adenosine in Feline Model of Acute Myocardial Ischemia-Reperfusion

BACKGROUND: Reestabilshment of blood flow is a standard therapeutic modality to salvage the myocardium at risk in an acute phase of myocardial infarction. However, there are significant evidences that reperfusion per se may injure the potentially viable myocardium, and a number of pharmacological agents were tried to reduce this reperfusion injury. Adenosine, an endogenous vasodilator, is suggested to reduce repergusion inury. To evaluate the myocardial protective effect of adenosine, magnetic resonance spectroscopy with superscript P was applied to feline model of acute myocardial ischemia-reperfusion, as well as pathological examination. METHODS: Effects of adenosine on the recovery of high energy phosphorous metabolites during 90 minutes of reperfusion period following 90 minutes of left anterior descending coronary artery ligation were assessed by31P spectroscopy in 27 cats(10: control group, 8: adenosine I group, 9: adenosine II group). In adenosine groups 0.2 mg/kg/min of adenosine was infused intravenously for 90 minutes from 30 miniutes before reperfusion in group I, and from just before reperfusion in group II. The experiments were performed on a 4.7 T/30 cm Biospec MRS/MRI system and the MR signals were obtained by using inner-diameter 1.5 cm-sized doubly tuned surface coil. The size of the spectral peaks was measured by area integration method. RESULTS: 1) Phosphocreatine(PCr) decreased rapidly with progression of ischemia, and recovered in reperfusion period in each group. PCr values in the reperfusion period were significantly higher in adenosine group than those in control group, although there was no difference between adenosine group I and II. 2) ATP decreased with progression of ischemia, and recovered in reperfusion period in each group. ATP values in the reperfusion period were significantly higher in adenosine groups than those in control group, byt there was no difference between adenosine group I and II. 3) pH decreased uniformly with progression of ischemia and recovered in reperfusion period, showing no difference between control and adenosine groups. 4) PCr/ATP ratio, representing the potential of oxidative phosphorylation, dereased with progression of ischemia and increased in reperfusion period. PCr/ATP ratio showed no difference between control, adenosine I and II groups. 5) Risk area/left ventricle ratio was not different in control and adenosine groups. Infarct size/risk area and infarct size/left ventricle ratios were smaller in adenosine II than those in control group. Howerver no significant diffence was noticed between adenosine I and control, and between adenosine I and II group. CONCLUSION: Intravenous infusion of adenosine showed the tendency of reducing the infarct size in the feline model of acute myocardial ischemia-reperfusion, and adenosine could improve significantly the recovery of high energy phosphate metabolites. This myocardial pretective effect of adenosine is considered to be present mainly in the reperfusion period.

Effect of adenosine on recovery of phosphorous metabolites in acute myocardial ischemia-reperfusion : In vivo P MR spectroscopic assessment in cats

BACKGROUND: To evaluate the metabolic and pathological changes associated with myocardial ischemia-reperfusion, magnetic resonance spectroscopy with 31P was applied as well as pathological examination. METHODS: Effect of adenosine on the recovery of high energy phosphorous metabolites during the reperfusion period following 90 minutes of left anterior descending coronary artery(LAD) ligation was assessed by 31P spectroscopy in 13 cats(8 : control group, 5 : adenosine group). In adenosine group 0.2 mg/kg/min of adenosine was infused intravenously for 90 minutes from 30 minutes before reperfusion. The experiments were peformed on a 4.7 T/30cm Biospec MRS/MRI system(Bruker, Switzerland) and the MR signals were obtained by using innerdiameter 1.5 cm sized doubly tuned surface coil. The size of the spectral peaks was measured by area integration method. RESULTS: In control group, high energy phosphorous metabolites decreased continueously during the ischemic period revealing the lowest values at the end of the periods : 17.0% for PCr and 24.0% for ATP, PCr depleted below 50% of the baseline level immediately after the LAD ligation and ATP, after 15 minutes of ischemia. Therfore the depletion rate was faster in PCr change than in ATP. The recovery of the PCr and ATP occurred after reestablishment of blood flow showing, for example, 43.3% and 36.3% of the baseline levels after 10 minutes of reperfusion. After infusion of adenosine, there was a tendency of higher recovery rates of high energy phosphates than in control group. Recovery rates of PCr and ATP after 90 minutes of reperfusion, were 28.2%, 11.2% in control group and 38.3%, 18.6% in adnosine group, respectively. In adenosine grop, relative sizes of infarction were not statistically different from those of control group. CONCLUSIONS: 31P MRS can be used for in-vivo assessment of the changes of high energy phosphorous metablites concerning acute myocardial ischemia and reperfusion. Adenosine infusion improves the recovery of ATP and PCr during the reperfusion period following acute ischemia.

Comparative of P spectroscopy and histochemical mapping in myocardial infarction in cats

This study was performed to assess the accuracy of 31P magnetic resonance spectroscopy(MRS) in the evaluation of myocardial ischemia in cats. Twelve cats underwent myocardial ischemia and reperfusion induced by 90 minutes ligation followed by 90 minutes recirculation of the left anterior descending coronary artery (LAD). MRS was performed using a 4.7T Biospec MRS/MRI system (Bruker, Switzerland). An inner diameter 1.5cm-sized doubly tuned surface coli was used for the collection of the MR signal. The coli was implanted to the epicardial surface at the expected area of infarction. 31P MRS was acquired before and during the periods of ischemia and reperfusion with 5-minute to 30-minute of intervals. After completion of the 31P MRS study, animals were sacrificed and the hearts were excised for 2,3,5-triphenyl tetrazolium chloride (TTG0 histochemical staining. The area of infarct was measured on the photographs of TTG stained heart slices using a computer programmed planimetry and the results were compared with those of the 31P MRS study. The level of phosphocreatine (PCr) was decreased to 28.2±6.9% of the baseline level 90 minutes after occlusion and recovered to 43.8±4.8% of the baseline level at the end of the reperfusion. A 50% depletion of PCr was reached 5 minutes after the LAD occlusion. The ATP was decreased to a 26.6±3.6% of the baseline level 90 minutes after occlusion and recovered to a 35.9±6.0 of the baseline level 90 minutes after reperfusion. The decreasing rate of ATP was slower than that of PCr showing a 50% of depletion 15 minutes after occlusion. The PCr/ATP ratio was 1.16±0.09 at the baseline, decreased to 0.88±0.07 at 30 minutes of occlusion, and then progressively increased during the late ischemic and reperfused periods. The ratio of the infarcted area to the effective signal area of the surface coli was inversely correlated to the ATP (r=0.68) and PCr (r=0.40) levels obtained at the end of reperfusion. In conclusion, 31P MRS reflects the changes in myocardial high energy phosphorous metabolism during the actue ischemia and reperfusion. If on adequate localization technique is feasible, 31P MRS can be used clinically in the diagnosis and monitoring of the patients with acute myocardial infarction.

In vitro 31P NMR spectroscopic assessment of the endurance and recovery capacity of skeletal muscle: comparison between the sedentaries and canoe athletes

In vivo 31P NMR spectroscopic study of forearm wrist flexor muscles was performed in two groups of volunteers composed respectively of 6 sedentaries and 6 canoe athletes. A continuous isometric contraction of endurance exercises was adopted in oder to assess the endurance capacity and recovery potential of skeletal muscles. Differences in high energy phosphorus metabolism between the sedentaries and athletes were evaluated with and emphasis on the intracellular pH and Pi/PCr ratio as indicators of high energy phosphorus metabolism. There were no differences of baseline pH and Pi/PCr ratio between the two groups. The athletes sustained the exercise at more acidic intracellular pH and at a higher Pi/PCr ratio of intracellular conditions for an all-out than did the sedentaries. The recovery rate of pH showed no difference between the two groups. There was a tendency of faster recovery of Pi/PCr in athletes showing half recovery time(T1/2) of 39.0±3.0 seconds as compared to that of sedentaries (55.7±7.5 seconds). The recovery rate of Pi/PCr as a function of Pi/PCr ratio at a given period of time was significantly faster in athletes than in sedentaries (P<0.001). The correlation coefficient of the recovery rate of Pi/PCr against the Pi/PCr ratio was 0.985 and 0.914 respectively for the athletes and sedentaries. The pH and the Pi/PCR ratio at an all-out state can be used as indicators of endurance capacity and the recovery rate of Pi/PCr, as a reovery potential of skeletal muscles.