In vivo 31P magnetic resonance spectroscopy using a needle microcoil

Batch fabrication methods have been used to produce low‐cost microcoils for magnetic resonance spectroscopy (MRS) that could be discarded after applications such as insertion into tissue during interventional surgery. Needle‐shaped microcoils were constructed using electroplated conductors buried in shafts formed with different combinations of silicon and plastic and used to acquire in vivo ³¹P spectra of rat thigh muscle at 81 MHz. The designs in this study achieved a maximum signal‐to‐noise ratio (SNR) for phosphocreatine (PCr) of 10.4 in a 10‐min acquisition, with the three adenosine triphosphate (ATP) multiplets also clearly visible. An average 20% reduction in PCr occurred over a 60‐min period, and intracellular pH was estimated to be 6.6, which are both evidence of ischemia. A needle microcoil design could have applications in real‐time MRS of tumors or in evaluating pathology in general during surgical investigations. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

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.     

Three-dimensional 31P magnetic resonance spectroscopic imaging of regional high-energy phosphate metabolism in injured rat heart

The purpose of this study was to measure the spatially varying ³¹P MR signals in global and regional ischemic injury in the isolated, perfused rat heart. Chronic myocardial infarcts were induced by occluding the left anterior descending coronary artery eight weeks before the MR examination. The effects of acute global low-flow ischemia were observed by reducing the perfusate flow. Chemical shift imaging (CSI) with three spatial dimensions was used to obtain ³¹P spectra in 54-/μl voxels. Multislice ¹H imaging with magnetization transfer contrast enhancement provided anatomical information. In normal hearts (n = 8), a homogeneous distribution of high-energy phosphate metabolites (HEP) was found. In chronic myocardial infarction (n = 6), scar tissue contained negligible amounts of HEP, but their distribution in residual myocardium was uniform. The size of the infarcted area could be measured from the metabolic images; the correlation of infarct sizes determined by histology and ³¹P MR CSI was excellent (P < 0.006). In global low-flow ischemia (n = 8), changes of HEP showed substantial regional heterogeneity. Three-dimensional ³¹P MR CSI should yield new insights into the regionally distinct metabolic consequences of various forms of myocardial injury.     

MR测定颈动脉易损斑块特征与急性缺血性脑卒中的关系

目的 分析急性缺血性脑卒中患者症状侧颈动脉粥样硬化病变特征与扩散加权成像(DWI)证实的急性脑梗死(ACI)发生及严重程度的关联性.方法 入组发生单侧肢体症状(颈内动脉供血区)的ACI患者103例,均在发病后1周内行颈动脉磁共振黑血成像(MR-BBI)及头颅常规MRI,测得症状侧颈动脉粥样硬化病变参数(管腔狭窄率、斑块负荷和成分)和相应供血区ACI病灶分布及大小,借此分析症状侧颈动脉斑块特征与ACI发生、大小的关联程度.结果 研究发现,症状侧颈动脉管壁体积标准化指数(PWV)及富脂质核(LRNC)含量是同侧供血区ACI病灶发生及大小的独立危险因素(校正管腔狭窄和临床因素前后,P<0.05).结论 ACI发生及大小与同侧供血颈动脉的斑块易损特征(高斑块负荷和大LRNC)相关联.MR-BBI能细致化评估斑块易损特征,有利于临床分层急性缺血性脑卒中的风险性及严重程度.     

Magnetic resonance imaging of experimental atherosclerotic plaque: comparison of two ultrasmall superparamagnetic particles of iron oxide

PURPOSE: To evaluate a new ultrasmall superparamagnetic particles of iron oxide (USPIO) compound, ferumoxytol, as a marker of macrophage activity in atherosclerotic plaques and to compare it to ferumoxtran-10. MATERIALS AND METHODS: Ten mature heritable hyperlipidemic (WHHL) female Watanabe rabbits served as the animal model for atherosclerosis, four coeval female New Zealand White (NZW) rabbits were the control group. Five WHHL and two NZW received a single intravenous injection (250 micromol/kg) of either ferumoxtran-10 or ferumoxytol and were subjected to daily MR examinations on a 1.5T whole body scanner for the next five days. Development of signal intensity changes and susceptibility effects was assessed. Statistical analysis was based on a nonparametric Wilcoxon-Mann-Whitney-U test by using a P value at the 0.05 significance level. On day 5, the rabbits were sacrificed and the aorta was referred to histopathology, distribution of iron particles in the vessel wall was analyzed. RESULTS: MRI was feasible in all animals. Three days after injection of ferumoxytol the highest luminal signal intensity measurements were observed in the ferumoxytol group; the highest measurements were five days after injection in the ferumoxtran-10 group (P < 0.05). In the WHHL, susceptibility effects presented as homogeneous dark lines parallel to the aortic wall after ferumoxytol and spotted areas void of signal after ferumoxtran-10. None of these findings were observed in the NZW control groups. CONCLUSION: Ferumoxtran-10 and ferumoxytol at a respective dose of 250 mumol/kg appear well suited for atherosclerotic plaque detection with MRI in experimental atherosclerosis. Ferumoxytol warrants further analysis in humans.     

Characterization of atherosclerotic plaque of carotid arteries with histopathological correlation: vascular wall MR imaging vs. color Doppler ultrasonography (US)

PURPOSE: To investigate whether the vessel wall MRI of carotid arteries would differentiate at-risk soft plaque from solid fibrous plaque by identifying liquid components more accurately than color Doppler ultrasonography (US). MATERIALS AND METHODS: This study included 54 carotid arteries in 54 consecutive patients who underwent carotid endarterectomy. MRI was performed using black-blood fat-suppressed (FS) T1-and FS T2-weighted TSE sequences. A total of 68 major segments of the 54 carotid plaques were grouped into four MR categories based on signal intensity index (SII). MR criteria used for the diagnosis of plaque vulnerability were: at-risk soft plaque including a segment of liquid component (category A or B), solid fibrous plaque (category C or D). The MR and US findings were compared with histopathological findings of endarterectomy specimens. RESULTS: Intraoperative findings and microscopic examination of endarterectomy specimens revealed 24 at-risk soft plaques and 30 solid fibrous plaques. The sensitivity, specificity, and accuracy for diagnosing at-risk soft plaque are 96%, 93%, and 94% for MR, and 75%, 63%, and 69% for color Doppler US, respectively. The slice-by-slice MR evaluation of carotid wall also revealed detailed information of plaque segments and correlated well with the features of corresponding histologic sections. CONCLUSION: Vessel wall MRI with MRI category could have a potential to more accurately diagnose an at-risk soft plaque predominantly composed of liquid components in comparison with color Doppler US.     

Reader and platform reproducibility for quantitative assessment of carotid atherosclerotic plaque using 1.5T Siemens, Philips, and General Electric scanners

PURPOSE: To evaluate the platform and reader reproducibility of quantitative carotid plaque measurements. MATERIALS AND METHODS: A total of 32 individuals with >or=15% carotid stenosis by duplex ultrasound were each imaged once by a 1.5T General Electric (GE) whole body scanner and twice by either a 1.5T Philips scanner or a 1.5T Siemens scanner. A standardized multisequence protocol and identical phased-array carotid coils were used. Expert readers, blinded to subject information, scanner type, and time point, measured the lumen, wall, and total vessel areas and determined the modified American Heart Association lesion type (AHA-LT) on the cross-sectional images. RESULTS: AHA-LT was consistently identified across the same (kappa = 0.75) and different scan platforms (kappa = 0.75). Furthermore, scan-rescan coefficients of variation (CV) of wall area measurements on Siemens and Philips scanners ranged from 6.3% to 7.5%. However, wall area measurements differed between Philips and GE (P = 0.003) and between Siemens and GE (P = 0.05). In general, intrareader reproducibility was higher than interreader reproducibility for AHA-LT identification as well as for quantitative measurements. CONCLUSION: All three scanners produced images that allowed AHA-LT to be consistently identified. Reproducibility of quantitative measurements by Siemens and Philips scanners were comparable to previous studies using 1.5T GE scanners. However, bias was introduced with each scanner and the use of different readers substantially increased variability. We therefore recommend using the same platform and the same reader for scans of individual subjects undergoing serial assessment of carotid atherosclerosis.     

Fast 31P chemical shift imaging using SSFP methods.

Steady-state free precession (SSFP) methods have been very successful due to their high signal and short imaging times. These properties make them good candidates for applications that intrinsically suffer from low signal such as low gamma nuclei imaging. A new chemical shift imaging (CSI) technique based on the SSFP signal formation has been implemented and applied to (31)P. The signal properties of the SSFP CSI method have been evaluated and the steady-state signal of (31)P has been measured in human muscles. Due to the T(2) and T(1) signal dependence of SSFP, the steady-state signal mainly consists of phosphocreatine (PCr). The technique allows fast CSI acquisitions with high SNR of the PCr signal. The SNR gain for PCr over a FLASH-based CSI method is approx. 4-5. Fast in vivo CSI of human muscle with subcentimeter resolution and high SNR is demonstrated at 2 T.     

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.     

Stiffness-weighted magnetic resonance imaging.

An imaging method is introduced in which the signal in MR images is affected by the stiffness distribution in the object being imaged. Intravoxel phase dispersion (IVPD) that occurs during MR elastography (MRE) acquisitions decreases the signal in soft regions more than in stiff regions due to changes in shear wave amplitude and wavelength. The IVPD effect is enhanced by lowpass filtering the MR k-space data with a circular Gaussian lowpass filter. A processing method is introduced to take the time series of MRE magnitude images with IVPD and produce a final stiffness-weighted image (SWI) by calculating the minimum signal at each pixel from a small number of temporal samples. The SWI technique is demonstrated in phantom studies as well as in the case of a preserved postmortem breast tissue specimen with a stiff lesion created by focused ultrasound ablation to mimic a breast cancer. When free of significant sources of depth-dependent wave attenuation, interference, and boundary effects, SWI is a simple, fast, qualitative technique that does not require the use of phase unwrapping or inversion algorithms for localizing stiff regions in an object.     

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.     

Comparison of 2D and multislab 3D magnetic resonance techniques for measuring carotid wall volumes

Purpose

To compare a multislab three‐dimensional volume‐selective fast spin‐echo (FSE) magnetic resonance (MR) sequence with a routine two‐dimensional FSE sequence for quantification of carotid wall volume.

Materials and Methods

One hundred normal subjects (50 men, mean age 44.6 years) underwent carotid vessel wall MR using 2D and 3D techniques. Carotid artery total vessel volume, lumen volume, wall volume, and wall/outer wall (W/OW) ratio were measured over 20 contiguous slices. Two‐ (2D) and three‐dimensional (3D) results were compared.

Results

The mean difference between 2D and 3D datasets (as a percentage of the mean absolute value) was 1.7% for vessel volume, 4.9% for lumen volume, 4.7% for wall volume, and 5.8% for W/OW ratio. There was good correlation between 2D and 3D models for total vessel volume (R² = 0.93, P < 0.001), lumen area (R² = 0.92, P < 0.001), and wall volume (R² = 0.77, P < 0.001). The correlation for the W/OW ratio was weaker (R² = 0.30; P < 0.001). The signal‐to‐noise ratio (SNR) for the 3D technique was 2.1‐fold greater than for the 2D technique (P < 0.001). When using the 3D sequence, scan time was reduced by 63%.

Conclusion

Multislab volume selective 3D FSE carotid arterial wall imaging performs similarly to a conventional 2D technique, but with over twice the SNR and substantially reduced scan time. J. Magn. Reson. Imaging 2008;28:1476–1482. © 2008 Wiley‐Liss, Inc.     

The impact of spatial resolution and respiratory motion on MR imaging of atherosclerotic plaque

PURPOSE: To examine the impact of spatial resolution and respiratory motion on the ability to accurately measure atherosclerotic plaque burden and to visually identify atherosclerotic plaque composition. MATERIALS AND METHODS: Numerical simulations of the Bloch equations and vessel wall phantom studies were performed for different spatial resolutions by incrementally increasing the field of view. In addition, respiratory motion was simulated based on a measured physiologic breathing pattern. RESULTS: While a spatial resolution of > or = 6 pixels across the wall does not result in significant errors, a resolution of < or = 4 pixels across the wall leads to an overestimation of > 20%. Using a double-inversion T2-weighted turbo spin echo sequence, a resolution of 1 pixel across equally thick tissue layers (fibrous cap, lipid, smooth muscle) and a respiratory motion correction precision (gating window) of three times the thickness of the tissue layer allow for characterization of the different coronary wall components. CONCLUSIONS: We found that measurements in low-resolution black blood images tend to overestimate vessel wall area and underestimate lumen area.     

Three-dimensional magnetic resonance imaging technique for myocardial-delayed hyperenhancement: a comparison with the two-dimensional technique

PURPOSE: To compare two-dimensional and three-dimensional techniques in the detection of myocardial infarction (MI) and in the grading transmural extent (TE). MATERIALS AND METHODS: Twelve patients with clinically proven MI were examined using two-dimensional and three-dimensional techniques with cardiac-gated, breath-hold, T1-weighted gradient echo sequence with an inversion recovery pulse following gadopentetate dimeglumine (Gd-DTPA) at 0.2 mmol/kg. Contrast-to-noise, signal-to-noise, and signal intensity ratios (CNR, SNR, and SIR, respectively) were derived and compared for each technique. RESULTS: From two-dimensional to three-dimensional, statistical significant difference was found in the mean CNR (11.65 vs. 56.59; P = 0.002), SNR (18.03 vs. 76.90; P < 0.001), and SIR (3.6 vs. 6.36; P = 0.05). Intraobserver agreement (kappa) between two-dimensional and three-dimensional were R1 = 74% and R2 = 90%. Interobserver agreements between the readers were two-dimensional = 77% and three-dimensional = 79%. CONCLUSION: Mean CNR, SNR, and SIR are significantly increased in the three-dimensional technique compared to the conventional two-dimensional technique.     

Scan‐rescan reproducibility of carotid atherosclerotic plaque morphology and tissue composition measurements using multicontrast MRI at 3T

Purpose:

To evaluate interscan reproducibility of both vessel morphology and tissue composition measurements of carotid atherosclerosis using a fast, optimized, 3T multicontrast protocol.

Materials and Methods:

A total of 20 patients with carotid stenosis >15% identified by duplex ultrasound were recruited for two independent 3T MRI (Philips) scans within one month. A multicontrast protocol including five MR sequences was applied: TOF, T1‐/T2‐/PD‐weighted and magnetization‐prepared rapid acquisition gradient‐echo (MP‐RAGE). Carotid artery morphology (wall volume, lumen volume, total vessel volume, normalized wall index, and mean/maximum wall thickness) and plaque component size (lipid rich/necrotic core, calcification, and hemorrhage) were measured over two time points.

Results:

After exclusion of images with poor image quality, 257 matched locations from 18 subjects were available for analysis. For the quantitative carotid morphology measurements, coefficient of variation (CV) ranged from 2% to 15% and intraclass correlation coefficient (ICC) ranged from 0.87 to 0.99. Except for maximum wall thickness (ICC = 0.87), all ICC were larger than 0.90. For the quantitative plaque composition measurements, the ICC of the volume and relative content of lipid rich/necrotic core and calcification were larger than 0.90 with CV ranging from 22% to 32%.

Conclusion:

The results from the multicontrast high‐resolution 3T MR study show high reliability for carotid morphology and plaque component measurements. 3T MRI is a reliable tool for longitudinal clinical trials, with shorter scan time compared to 1.5T. J. Magn. Reson. Imaging 2010;31:168–176. © 2009 Wiley‐Liss, Inc.     

Quantification of human atherosclerotic plaques using spatially enhanced cluster analysis of multicontrast-weighted magnetic resonance images.

One of the current limitations of magnetic resonance imaging (MRI) is the lack of an objective method to classify plaque components. Here we present a cluster analysis technique that can objectively quantify and classify MR images of atherosclerotic plaques. We obtained three-dimensional (3D) images from 12 human coronary artery specimens on a 9.4T imaging system using multicontrast-weighted fast spin-echo (T1-, proton density-, and T2-weighted) imaging with an isotropic voxel size of 39 micro. Spatially enhanced cluster analysis (SECA) was performed on multicontrast MR images, and the resulting segmentation was evaluated against histological tracings. To visualize the overall structure of plaques, the MR images were rendered in 3D. The specimens exhibited lesions of American Heart Association (AHA) plaque classification types I-VI. Both MR images and histological sections were independently reviewed, categorized, and compared. Overall, the classification obtained from the cluster-analyzed MR and histopathology images showed very good agreement for all AHA types (92%, Cohen's kappa = 0.89, P < 0.0001). All plaque types were identified and quantified by SECA with a high degree of correlation between cluster-analyzed MR and manually traced histopathology data. MRI combined with SECA provides an objective method for atherosclerotic plaque component characterization and quantification.     

In vivo detection of hemorrhage in human atherosclerotic plaques with magnetic resonance imaging

PURPOSE: To investigate the performance of high-resolution T1-weighted (T1w) turbo field echo (TFE) magnetic resonance imaging (MRI) for the identification of the high-risk component intraplaque hemorrhage, which is described in the literature as a troublesome component to detect. MATERIALS AND METHODS: An MRI scan was performed preoperatively on 11 patients who underwent carotid endarterectomy because of symptomatic carotid disease with a stenosis larger than 70%. A commonly used double inversion recovery (DIR) T1w turbo spin echo (TSE) served as the T1w control for the T1w TFE pulse sequence. The MR images were matched slice by slice with histology, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the MR images were calculated. Additionally, two readers, who were blinded for the histological results, independently assessed the MR slices concerning the presence of intraplaque hemorrhage. RESULTS: More than 80% of the histological proven intraplaque hemorrhage could be detected using the TFE sequence with a high interobserver agreement (Kappa = 0.73). The TFE sequence proved to be superior to the TSE sequence concerning SNR and CNR, but also in the qualitative detection of intraplaque hemorrhage. The false positive TFE results contained fibrous tissue and were all located outside the main plaque area. CONCLUSION: The present study shows that in vivo high-resolution T1w TFE MRI can identify the high-risk component intraplaque hemorrhage with a high detection rate in patients with symptomatic carotid disease. Larger clinical trials are warranted to investigate whether this technique can identify patients at risk for an ischemic attack.     

Quantitative 31P magnetic resonance spectroscopy of the human breast at 7 T

This study presents quantified levels of phosphorylated metabolites in glandular tissue of human breast using (31)P magnetic resonance spectroscopy at 7 T. We used a homebuilt (1)H/(31)P radiofrequency coil to obtain artifact-free (31)P MR spectra of glandular tissue of healthy females by deploying whole breast free induction decay (FID) detection with adiabatic excitation and outer volume suppression. Using progressive saturation, the estimated apparent T(1) relaxation time of (31)P spins of phosphocholine and phosphoethanolamine was 4.4 and 5.7 s, respectively. Quantitative measures for phosphocholine and phosphoethanolamine levels in glandular tissue were established based on MR imaging. We used a 3D (1)H image of the breast to segment the glandular tissue; this was matched to a 3D (31)P image of the B1- field of the (31)P coil to correct for differences in glandular tissue volume and B(1) inhomogeneity of the (31)P coil. The (31)P MR spectra were calibrated using a phantom with known concentration. Average levels of phosphocholine and phosphoethanolamine in 11 volunteers were 0.84 ± 0.21 mM and 1.18 ± 0.41 mM, respectively. In addition, data of three patients with breast cancer showed higher levels of phosphocholine and phosphoethanolamine compared with healthy volunteers. This may indicate a potential role for the use of (31)P magnetic resonance spectroscopy for characterization, prognosis, and treatment monitoring in breast cancer.     

High-resolution MRI with cardiac and respiratory gating allows for accurate in vivo atherosclerotic plaque visualization in the murine aortic arch.

Genetically engineered mouse models provide enormous potential for investigation of the underlying mechanisms of atherosclerotic disease, but noninvasive imaging methods for analysis of atherosclerosis in mice are currently limited. This study aimed to demonstrate the feasibility of MRI to noninvasively visualize atherosclerotic plaques in the thoracic aorta in mice deficient in apolipoprotein-E, who develop atherosclerotic lesions similar to those observed in humans. To freeze motion, MR data acquisition was both ECG- and respiratory-gated. T(1)-weighted MR images were acquired with TR/TE approximately 1000/10 ms. Spatial image resolution was 49 x 98 x 300 micro m(3). MRI revealed a detailed view of the lumen and the vessel wall of the entire thoracic aorta. Comparison of MRI with corresponding cross-sectional histopathology showed excellent agreement of aortic vessel wall area (r = 0.97). Hence, noninvasive MRI should allow new insights into the mechanisms involved in progression and regression of atherosclerotic disease.