31P-MR spectroscopic imaging in hypertensive heart disease

Hypertensive heart disease (HHD) causes structural changes (e.g., fibrosis) that result in diastolic and systolic myocardial dysfunction. Alterations of ³¹P metabolism and cardiac energy impairments were assessed in patients with HHD by MR spectroscopy (MRS) and correlated with left ventricular systolic function. Thirty-six patients with HHD and 20 healthy controls (mean age 35.2±10.7 years) were examined with ³¹P-MRS at 1.5 T by using an ECG-gated CSI sequence. Twenty-five patients (mean age 64.3±9.3 years) had diastolic dysfunction, but preserved systolic function (HHD-D), whereas 11 patients (62.3±11.4 years) suffered from additional impaired systolic function (HHD-S). In both patient groups, the PCr/γ-ATP ratio was lower than in the controls (controls: 2.07±0.17; P<0.001), and in HHD-S was lower than in HHD-D (1.43±0.21 vs. 1.65±0.25; P=0.012). PCr/γ-ATP ratios were linearly correlated with LVEF (Pearson's r: 0.39; P=0.025). In the HHD-S group, the PDE/γ-ATP ratio was significantly lower (0.56±0.36) than in the controls (1.14±0.42; P=0.001). In contrast to the group of HHD-D patients, whose slightly decreased PCr/γ-ATP ratios compared to controls may be explained by age differences, the more distinct changes observed in HHD-S patients indicate an altered energy metabolism. The observed metabolic changes were related to functional impairments, as indicated by a reduced LVEF. Reduced PDE/ATP ratios indicate changes in the phospholipid metabolism.     

Metabolic imaging of atrophic muscle tissue using appropriate markers in 1H and 31P NMR spectroscopy

Introduction The purpose of this feasibility study was to demonstrate non-invasive metabolic imaging of human muscular atrophy using significant changes of NMR signals that are related directly or indirectly to fiber necrosis.Methods Single-voxel ¹H NMR spectroscopy and two-dimensional ³¹P spectroscopic imaging on a 1.5-T whole-body scanner were used for in vivo mapping of areas of muscle damage in two cases of differently localized and pronounced atrophy. Spectral patterns affiliated with severe and intermediate stages of degeneration were compared to data of healthy control tissue to derive appropriate metabolic markers related to lipid infiltration or high-energy ³¹P metabolism.Results Reliable detection of atrophic tissue was achieved by the following parameters: (1) liposclerotic turnover is related to a drastic reduction in the water/lipid ¹H signal intensity ratio (up to a factor of 74 compared to adjacent healthy tissue); (2) the ³¹P resonance of phosphocreatine (PCr) is an adequate marker for differentiation of intact myocells with high-energy metabolism from regions dominated by terminal fiber necrosis (PCr signal vanished nearly completely or intensity was reduced by a factor of 3 in affected muscles). Metabolic images based on this signal allowed accurate non-invasive localization of atrophic tissue.Conclusion The molecular information provided by NMR spectroscopy—previously only used with poor localization in atrophy studies—enables access to both the myocell-specific high-energy metabolism and the result of lipid infiltration allowing non-invasive mapping of degenerate tissue. The ability to investigate the results of these advanced levels of atrophy would also be useful for studies of more subtle degrees of denervation.     

In vivo 31P magnetic resonance spectroscopy of human brain at 7 T: an initial experience.

In vivo (31)P spectra were acquired from the human primary visual cortex at 7 T. The relaxation times of the cerebral metabolites, intracellular pH, rate constant (k(f)) of the creatine kinase (CK) reaction, and nuclear Overhauser enhancement (NOE) on the detected phosphorus moieties from irradiation of the water spins were measured from normal subjects. With a 5-cm-diameter surface coil, 3D (31)P chemical shift imaging was performed with a spatial resolution of 7.5 ml and an acquisition resolution of 8 min, resulting in a signal-to-noise ratio (SNR) for phosphocreatine (PCr) resonance of 32. The apparent T(1) and T(2) of PCr measured at 7 T were 3.37 +/- 0.29 s and 132.0 +/- 12.8 ms, respectively, which were considerably longer than those of adenosine triphosphate (ATP) (T(1): 1.02-1.27 s; T(2): 25-26 ms). The NOE measured in this study was 24.3% +/- 1.6% for PCr, and 10% for ATP. The k(f) measured in the human primary visual cortex was 0.24 +/- 0.03 s(-1). The results from this study suggest that ultra-high-field strength is advantageous for performing in vivo (31)P magnetic resonance spectroscopy (MRS) in the human brain.     

Duchenne型肌营养不良患者长期服用激素对白内障和眼压的影响

目的 分析杜氏肌营养不良症(Duchenne muscular dystrophy,DMD)患者长期服用激素对白内障、眼压的影响及白内障、高眼压发生的危险因素.方法 回顾性分析2018-08至2020-12就诊于解放军总医院第三医学中心具有详细眼科检查的158例DMD患者临床资料.根据长期(≥6个月)是否服用激素,将患...     

Comparisons of ATP turnover in human muscle during ischemic and aerobic exercise using 31P magnetic resonance spectroscopy

To investigate human muscle bioenergetics quantitatively in vivo, we used ³¹P magnetic resonance spectroscopy to study the flexor digitorum superficialis of four adult males during dynamic ischemic and aerobic exercise at 0.50–1.00 W and during recovery from aerobic exercise. During exercise, changes in pH and [PCr] were larger at higher power, but in aerobic exercise neither end-exercise [ADP] nor the initial postexercise PCr resynthesis rate altered with power. In ischemic exercise we estimated total ATP synthesis from the rates of PCr depletion and glycogenolysis (inferred using an analysis of proton buffering); this was linear with power output. In aerobic exercise, again we estimated ATP synthesis rates due to phosphocreatine hydrolysis and glycogenolysis (incorporating a correction for proton efflux) and also estimated oxidative ATP synthesis by difference, using the total ATP turnover rate established during ischemic exercise. We conclude that in early exercise oxidative ATP synthesis was small, increasing by the end of exercise to a value close (as predicted) to the initial postexercise rate of PCr resynthesis. Furthermore, a plausible estimate of proton efflux during aerobic exercise can be inferred from the pH-dependence of proton efflux in recovery.     

~(31)P磁共振波谱回顾及其在肝脏等脏器中的临床应用

常规方法检测肝脏ATP需要大量组织标本 ,在同一批动物或人体的重复检测是不可能的 ,并且不能监测早期或可逆性细胞损伤中的轻微新陈代谢变化。3 1PMRS是活体检测高能磷酸盐的唯一手段。无机磷 (Pi)与磷酸单酯 (PME)比率 (细胞生存和代谢的标志 )以及各种ATP可以重复定量检测。在细胞死亡和随后的器官病变之前 ,利用3 1PMRS ,可检测到早期轻微能量变化引起的β ATP明显减少 ,Pi/ β ATP比率减少以及PME/ β ATP比率的显著升高[1] 。在正常肝脏的波谱中 ,含磷总量的PME波峰为 4 .77% (可信区间CI:4 .11～ 5 .4 2 ) ,在轻度肝硬化 [5 .80 % (95 %CI:5 .4 6～ 6 .14 ) ,P =0 0 0 5 1,对正常肝 ]和重度肝硬化 [9.6 4 % (95 %CI:8.71～ 10 .5 7) ,P =0 .0 0 0 2 ,对正常肝和P =0 .0 0 1,对轻度肝硬化 ]明显升高[2 ] 。在对所有原发或继发肿瘤患者的研究中 ,PME/PDE比率是增加的 ,作者认为3 1PMRS是检测肝脏疾病进展和治疗效果的有效方法[3 ] 。     

In vivo and in vitro 31P magnetic resonance spectroscopic studies of the hepatic response of healthy rats and rats with acute hepatic damage to fructose loading

The hepatic response to a fructose challenge for control rats, and rats subjected to an acute sublethal dose of carbon tetrachloride (CCI₄) or bromobenzene (BB), was compared using dynamic in vivo ³¹P MRS. Fructose loading conditions were used in which control rats showed only a modest increase in hepatic phosphomonoester (PME), and a small decrease in ATP, P_i, and intracellular pH after fructose administration. Both CCI₄, and BB-treated rats showed a much greater fructose-induced accumulation of PME than did controls. Trolox C, a free radical scavenger, prevented most of this PME increase. BB-treated rats, given sufficient time to recover from the hepa-totoxic insult, responded to the fructose load similarly to controls. Liver aldolase activities of control, toxicant-treated rats, and toxicant plus Trolox C-treated rats correlated inversely with PME accumulation after fructose loading (correlation coefficient: ?0.834, P < 0.05). Perchloric acid extracts of rat livers studied by in vitro ³¹P MRS confirmed that the PME accumulation after fructose loading is mainly due to an increase in fructose 1-phosphate. These studies are consistent with the aldolase-catalyzed cleavage of fructose 1-phosphate being rate-limiting in hepatic fructose metabolism, and that the CCI, and BB treatment modify and inactivate the aldolase enzyme.     

Optimized detection of changes in glucose-6-phosphate levels in human skeletal muscle by 31P MR spectroscopy.

As glucose-6-phosphate (G6P) plays a central role in muscle energy metabolism, the possibility to observe changes in the tissue level of this compound in vivo is very relevant. G6P can be detected noninvasively by (31)P MR spectroscopy, but its visibility in vivo is severely hampered due to low tissue levels and spectral overlap with other, stronger phosphomonoester signals. To optimize the observation of changes in G6P levels in human calf muscle by (31)P MR spectroscopy at 1.5 T, we implemented an approach involving a new RF probe and a postacquisition correction method. An anatomically shaped circularly polarized (31)P coil was designed for high intrinsic sensitivity. Together with an additional (1)H coil and (1)H blocking circuits this allowed the application of NOE and (1)H decoupling to further enhance sensitivity. A hyperglycemic hyperinsulinemic clamp was used to increase G6P levels. The spectra were corrected for frequency and phase drift due to scanner instability and leg movements using an automated phase and frequency correction method. Difference (31)P spectroscopy was applied to detect changes of the G6P signal. The result, in five healthy subjects, demonstrated that the combination of sensitivity optimization with automated drift correction enabled a robust detection of G6P changes in time series experiments down to a resolution of 10 min.     

P magnetic resonance spectroscopy to measure in vivo cardiac energetics in normal myocardium and hypertrophic cardiomyopathy: Experiences at 3 T

Background

³¹P magnetic resonance spectroscopy (MRS) allows measurement of in vivo high-energy phosphate kinetics in the myocardium. While traditionally ³¹P cardiac spectroscopy is performed at 1.5 T, cardiac MRS at higher field strength can theoretically increase signal to noise ratio (SNR) and spectral resolution therefore improving sensitivity and specificity of the cardiac spectra. The reproducibility and feasibility of performing cardiac spectroscopy at 3 T is presented here in this study in healthy volunteers and patients with hypertrophic cardiomyopathy.

Methods

Cardiac spectroscopy was performed using a Phillips 3T Achieva scanner in 37 healthy volunteers and 26 patients with hypertrophic cardiomyopathy (HCM) to test the feasibility of the protocol. To test the reproducibility a single volunteer was scanned eight times on separate occasions. A single voxel ³¹P MRS was performed using Image Selected In vivo Spectroscopy (ISIS) volume localization.

Results

The mean phosphocreatine/adenosine triphosphate (PCr/ATP) ratio of the eight measurements performed on one individual was 2.11 ± 0.25. Bland Altman plots showed a variance of 12% in the measurement of PCr/ATP ratios. The PCr/ATP ratio was significantly reduced in HCM patients compared to controls, 1.42 ± 0.51 and 2.11 ± 0.57, respectively, P < 0.0001. (All results are expressed as mean ± standard deviation).

Conclusions

Here we demonstrate that cardiac ³¹P MRS at 3 T is a reliable method of measuring in vivo high-energy phosphate kinetics in the myocardium for clinical studies and diagnostics. Based on our data an impairment of cardiac energetic state in patients with hypertrophic cardiomyopathy is indisputable.     

Epithelial and stromal metabolite changes in the transition from cervical intraepithelial neoplasia to cervical cancer: an in vivo 1H magnetic resonance spectroscopic imaging study with ex vivo correlation

To investigate epithelial and stromal metabolite changes in cervical intraepithelial neoplasia (CIN) and cervical cancer in vivo and correlate findings with MR spectroscopy of tissue samples. Forty-seven women (19 with CIN, 28 with cervical cancer) underwent endovaginal MR at 1.5 T with T2-W and localised 2D MR spectroscopic imaging (PRESS, TR = 1,500 ms, TE = 135 ms). tCho, 2 ppm and -CH₂ lipid peaks were measured in epithelial (>50% epithelium, no tumour), stromal (>50% stroma, no tumour) and tumour (>30% tumour) voxels. Unsuppressed water signal from the same voxel provided a concentration reference. ¹H HR-MAS MR spectra were acquired from tissue in 37 patients (11.74 T, pulse-acquire and cpmg sequences, with water pre-saturation). Analysable data from 17 CIN and 25 cancer patients showed significant increases in tCho (p = 0.03) and 2 ppm (p = 0.007) in tumour compared with epithelial voxels from CIN patients, but not with epithelial voxels from cancer patients. No significant differences were seen in stroma from cancer compared with CIN patients. Differences in -CH₂ lipids were not significant between groups. There was no significant correlation between in vivo and ex vivo tCho or -CH₂ lipids. Estimated in vivo concentrations of tCho and 2 ppm resonances increase in tumour and adjacent epithelium in progression from CIN to cervical cancer. This work was supported by Cancer Research UK (CUK) grant nos. C1353/A5408 and C1060/A808.     

Application of 31P NMR spectroscopy to monitor chemotherapy-associated changes of serum phospholipids in patients with malignant lymphomas

³¹P spectra were obtained from 22 healthy volunteers and 35 patients with malignant lymphomas. Sera from patients were collected at the time of diagnosis and at several time-points during therapy. Long-term follow-up studies showed a good correlation between the ³¹P NMR spectra of sera and the clinically evident response of the disease to the chemotherapy. During therapy leading to remission resonance from phospholipids increased progressively resulting in spectra similar to those seen in normal sera. By contrast, in patients who did not respond to therapy the intensities of the phospholipid peaks remained relatively low or became progressively reduced as the disease progressed. To understand the source of the spectral differences, we also examined the concentrations of high-density lipoprotein, low-density lipoprotein, cholesterol, and triglycerides. In individuals responding to the treatment, both high-density lipoprotein and cholesterol increased to the point where they were statistically equivalent to those from healthy volunteers.     

ATP production and mechanical work in exercising skeletal muscle: A theoretical analysis applied to 31P magnetic resonance spectroscopic studies of dialyzed uremic patients

³¹P magnetic resonance spectroscopy (³¹P MRS) can yield much information about bioenergetics in skeletal muscle. During mixed aerobic/glycolytic exercise, changes in phos-phocreatine (PCr) concentration and pH may be abnormal because of reduced muscle mass or reduced efficiency (which the authors combine here as “effective muscle mass”) or because of reduced oxidative capacity. The authors show how these can be distinguished by calculating the nonoxidative and oxidative costs of mechanical work, and also of work per unit of effective muscle mass (measured using the initial rate of ATP turnover). These quantities are substantially time-independent during incremental exercise, and so can be used to compare exercise studies of differing duration. The authors illustrate this analysis by showing that in dialyzed patients with chronic renal failure, the substantial exercise abnormalities seen by ³¹P MRS are due mainly to a decrease in effective muscle mass, which outweighs the oxidative defect implied by the abnormal PCr recovery kinetics.     

Applications of neural network analyses to in vivo 1H magnetic resonance spectroscopy of Parkinson disease patients

PURPOSE: To apply neural network analyses to in vivo magnetic resonance spectra of controls and Parkinson disease (PD) patients for the purpose of classification. MATERIALS AND METHODS: Ninety-seven in vivo proton magnetic resonance spectra of the basal ganglia were recorded from 31 patients with (PD) and 14 age-matched healthy volunteers on a 1.5-T imager. The PD patients were grouped as follows: probable PD (N = 15), possible PD (N = 11), and atypical PD (N = 5). Total acquisition times of approximately five minutes were achieved with a TE (echo time) of 135 msec, a TR (repetition time) of 2000 msec, and 128 scan averages. Neural network (back propagation, Kohonen, probabilistic, and radial basis function) and related (generative topographic mapping) data analyses were performed. RESULTS: Conventional data analysis showed no statistically significant differences in metabolite ratios based on measuring signal intensities. The trained networks could distinguish control from PD with considerable accuracy (true positive fraction 0.971, true negative fraction 0.933). When four classes were defined, approximately 88% of the predictions were correct. The multivariate analysis indicated metabolic changes in the basal ganglia in PD. CONCLUSION: A variety of neural network and related approaches can be successfully applied to both qualitative visualization and classification of in vivo spectra of PD patients.     

In vivo measurement of the hypoxia marker EF5 in Shionogi tumours using 19F magnetic resonance spectroscopy

Purpose:?¹⁹F magnetic resonance spectroscopy (MRS) was used to non-invasively detect EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] adducts in the Shionogi tumour model of prostate cancer to evaluate hypoxia.

Material and methods:?¹⁹F MRS signal of EF5 in Shionogi mouse tumours was acquired using a 2 cm diameter solenoid volume coil with a 7.05 T Bruker scanner. MRS signal was observed in mouse tumours longitudinally following intraperitoneal (IP) injection of EF5. Another mouse group was injected intravenously (IV) with EF5, and in vivo MRS signal was obtained two hours after injection. This data was compared with the ex vivo percentage of hypoxic cells present in the corresponding excised tumours, determined by flow cytometry of bound EF5.

Results:?Longitudinal ¹⁹F MRS signal attributable to EF5 began to decline within five hours of EF5 administration. Flow cytometry comparisons yielded an inverse correlation (p-value < 0.006) between the MRS signal and tumour hypoxic cell percentage. The tumours exhibited an average cell viability of 34 ± 26%.

Conclusions:?The results confirmed that MRS of EF5 in mice is an unsuitable technique for the determination of EF5 binding as a measure of tumour hypoxia.     

Finger printing of mycobacterium tuberculosis in patients with intracranial tuberculomas by using in vivo,ex vivo,and in vitro magnetic resonance spectroscopy

In vivo, ex vivo, and in vitro proton magnetic resonance spectroscopy was performed in 12 patients with intracranial tuberculomas with an aim of detecting the biochemical constituents of Mycobacterium tuberculosis in a granuloma. One dimensional (1D) single pulse and spin-echo sequences and 2D correlative spectroscopy were used for the ex vivo study to confirm the resonances seen on in vivo study. Spectroscopic studies of the perchloric acid and lipid extract of granuloma and M. tuberculosis were performed to look for similarity of resonance. In vivo study showed the presence of lipids at 0.9, 1.3, 2.0, 2.8 ppm, and phosphoserine at 3.7 ppm. All these resonances were confirmed on ex vivo study. In addition, distinct resonances of serine and phenolic lipids were seen on ex vivo and in vitro study of tuberculous granuloma, which have not been observed in other intracranial tumors. Lipid extract of granuloma and M. tuberculosis showed phenolic lipids at 7.1 and 7.4 ppm, a constituent of the cell wall of the bacteria in a tuberculoma. It appears that it may be possible to finger print the biochemicals of the cell wall of M. tuberculosis in a tuberculous granuloma and thus may help in detection and diagnosis of such lesions.     

Assessment of glucosylifosfamide mustard biodistribution in rats with prostate adenocarcinomas by means of in vivo 31P NMR and in vitro uptake experiments

A combined in vitro/in vivo study was performed to evaluate the possible application of phosphorus (³¹P) NMR spectros-copy for therapy monitoring and to investigate glucosylifos-famide mustard (Glc-IPM) transport and biodistribution by radiotracer techniques. Dynamic in vivo ³¹P NMR measurements were performed in rats with prostate adenocarcinoma after iv injection of 1 mmol/kg body weight (bw) of ifosfamide (IFO) (n = 4) and 1 mmol/kg bw (n = 4) or 2.15 mmol/kg bw (n = 9) of Glc-IPM. In a biodistribution study with ¹⁴C-labeled Glc-IPM and a final dose of 0.8 mmol Glc-IPM/kg bw, the animals were killed 5, 30, 60, and 120 min after drug administration, an ethanol extraction was performed from several tissues, and the dose per g tissue was calculated. The same tumor cell line was used in saturation and competition experiments to further elucidate the transport mechanism. The ³¹P NMR signals of IFO and Glc-IPM showed no overlap with the endogenous phosphorus peaks. A rapid washout with a half-life between 25.9 ± 5.6 min for the lower dose and 34.3 ± 4.2 min for the higher dose of Glc-IPM was observed in the tumor. No statistically significant change of the pH value was observed during the examination period. The β-nucleoside 5′-triphosphate (NTP)/inorganic phosphate (Pi) signal intensity ratio showed a tendency to decrease but without statistical significance. A rapid elimination was demonstrated by both the noninvasive NMR technique and the biodistribution study. No saturation was found in vitro for the Glc-IPM uptake, even at the concentration of 5 m/W. Furthermore, the Glc-IPM uptake was not inhibited by the presence of 2-deoxyglucose and vice versa. The data show that the pharmacokinetics of Glc-IPM in the tumor can be followed in vivo by ³¹P NMR. The results presented are evidence for diffusion as the transport mechanism for Glc-IPM in this tumor model. However, the better visualization of Glc-IPM as compared to ifosfamide may be due to metabolic trapping of a negatively charged metabolite after deglycosylation.     

Role of diffusion weighted imaging and proton magnetic resonance spectroscopy in ring enhancing brain lesions

Aim of the work

To assess and compare the usefulness and efficacy of both diffusion weighted imaging (DWI) and proton magnetic resonance spectroscopy (¹HMRS) in brain lesions with ring enhancement in post contrast T1WI and to determine which method is more effective.

Subjects and methods

Thirty patients with ring-enhanced brain lesions were classified into 2 groups, abscess group (11 patients) and tumor group (19 patients), were examined using diffusion-weighted imaging (DWI) and H-proton magnetic resonance spectroscopy (¹HMRS).

Results

Restricted diffusion and low ADC value were seen in 9 (81%) patients of brain abscesses, however, free diffusion and high ADC value were found in 18 (94%) patients with necrotic brain tumor. The abscess group showed aminoacids, acetate and lactate in 9 patients and extra peak of succinate was found in 1 patient; however in the tumor group lactate alone was found in 12 patients, lactate and choline were seen in 5 patients, none of the patients showed amino acids, succinate or acetate.

Conclusion

Both DWI and ¹HMRS are useful and efficient imaging techniques in ring enhancing brain lesions and differentiate between pyogenic brain abscesses and necrotic tumors, but DWI is accurate, has less imaging time than ¹HMRS, also is available in many imaging centers.     

An experimental study on acute brain radiation injury: Dynamic changes in proton magnetic resonance spectroscopy and the correlation with histopathology

Purpose

To investigate the correlation between the alterations of single-voxel ¹H MRS and the histopathological characteristics of radiation brain injury following radiation.

Materials and methods

Twenty-seven rabbits were randomized into nine groups to receive radiation with a single dose of 25 Gy. The observation time points included a pre-radiation and 1, 2, 3, 4, 5, 6, 7, and 8 wk following radiation. Each treatment group underwent conventional MRI and single-voxel ¹H MRS, N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were observed over the region of interest, and the presence or absence of lactate (Lac) and lipid (Lip) was detected. Histological specimens of each group were obtained after image acquisition.

Results

The values of Cho were significantly increased in the first 3 wk, and decreased over the following 5 wk after radiation. Levels of NAA showed a trend toward a decrease 5 wk after radiation. The levels of Cr were not changed between before and after radiation. The Cho/NAA metabolic ratio was significantly increased in weeks 6, 7, and 8 following irradiation, compared to pre-radiation values. Vascular and glial injury appeared on 2 wk after RT in the histology samples, until 4 wk after RT, necrosis of the oligodendrocytes, neuronal degeneration and demyelination could be observed.

Conclusions

MRS is sensitive to detect metabolic changes following radiation, and can be used in the early diagnosis of radiation brain injury.