Anatomical and functional brain imaging using high-resolution echo-planar spectroscopic imaging at 1.5 Tesla

High-resolution echo-planar spectroscopic imaging (EPSI) of water resonance (i.e. without water suppression) is proposed for anatomic and functional imaging of the human brain at 1.5 T. Water spectra with a resolution of 2.6 Hz and a bandwidth of 333 Hz were obtained in small voxels (1.7 x 1.7 x 3 mm3) across a single slice. Although water spectra appeared Lorentzian in most of the voxels in the brain, non-Lorentzian broadening of the water resonance was observed in voxels containing blood vessels. In functional experiments with a motor task, robust activation in motor cortices was observed in high-resolution T2* maps generated from the EPSI data. Shift of the water resonance frequency occurred during neuronal activation in motor cortices. The activation areas appeared to be more localized after excluding the voxels in which the lineshape of the water resonance had elevated T2* and became more non-Lorentzian during the motor task. These preliminary results suggest that high-resolution EPSI is a promising tool to study susceptibility-related effects, such as BOLD contrast, for improved anatomical and functional imaging of the brain.     

Nosologic imaging of the brain: segmentation and classification using MRI and MRSI

A new technique is presented to create nosologic images of the brain based on magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI). A nosologic image summarizes the presence of different tissues and lesions in a single image by color coding each voxel or pixel according to the histopathological class it is assigned to. The proposed technique applies advanced methods from image processing as well as pattern recognition to segment and classify brain tumors. First, a registered brain atlas and a subject‐specific abnormal tissue prior, obtained from MRSI data, are used for the segmentation. Next, the detected abnormal tissue is classified based on supervised pattern recognition methods. Class probabilities are also calculated for the segmented abnormal region. Compared to previous approaches, the new framework is more flexible and able to better exploit spatial information leading to improved nosologic images. The combined scheme offers a new way to produce high‐resolution nosologic images, representing tumor heterogeneity and class probabilities, which may help clinicians in decision making. Copyright © 2008 John Wiley & Sons, Ltd.     

Intraventricular temperature measured by diffusion‐weighted imaging compared with brain parenchymal temperature measured by MRS in vivo

We examined and compared the temperatures of the intraventricular cerebrospinal fluid (T_v) and the brain parenchyma (T_p) using MRI, with reference to the tympanic membrane temperature (T_t) in healthy subjects. We estimated T_v and T_p values from data gathered simultaneously by MR diffusion‐weighted imaging (DWI) and MRS, respectively, in 35 healthy volunteers (17 males, 18 females; age 25–78 years). We also obtained T_t values just before each MR examination to evaluate the relationships among the three temperatures. There were significant positive correlations between T_v and T_p (R = 0.611, p < 0.001). The correlation was also significant after correction for T_t (R = 0.642, p < 0.001). There was no significant correlation between T_v and T_t or between T_p and T_t in the men or the women. Negative correlations were found between T_v and age and between T_p and age in the males but not females. DWI thermometry seems to reflect the intracranial environment as accurately as MRS thermometry. An age‐dependent decline in temperature was evident in our male subjects by both DWI and MRS thermometry, probably due to the decrease in cerebral metabolism with age. Copyright © 2016 John Wiley & Sons, Ltd.     

Spatial variability and reproducibility of GABA‐edited MEGA‐LASER 3D‐MRSI in the brain at 3 T

The reproducibility of gamma‐aminobutyric acid (GABA) quantification results, obtained with MRSI, was determined on a 3 T MR scanner in healthy adults. In this study, a spiral‐encoded, GABA‐edited, MEGA‐LASER MRSI sequence with real‐time motion–scanner‐instability corrections was applied for robust 3D mapping of neurotransmitters in the brain. In particular, the GABA⁺ (i.e. GABA plus macromolecule contamination) and Glx (i.e. glutamate plus glutamine contamination) signal was measured. This sequence enables 3D‐MRSI with about 3 cm³ nominal resolution in about 20 min. Since reliable quantification of GABA is challenging, the spatial distribution of the inter‐subject and intra‐subject variability of GABA⁺ and Glx levels was studied via test–retest assessment in 14 healthy volunteers (seven men–seven women). For both inter‐subject and intra‐subject repeated measurement sessions a low coefficient of variation (CV) and a high intraclass correlation coefficient (ICC) were found for GABA⁺ and Glx ratios across all evaluated voxels (intra?/inter‐subject: GABA⁺ ratios, CV ~ 8%–ICC > 0.75; Glx ratios, CV ~ 6%–ICC > 0.70). The same was found in selected brain regions for Glx ratios versus GABA⁺ ratios (CV varied from about 5% versus about 8% in occipital and parietal regions, to about 8% versus about 10% in the frontal area, thalamus, and basal ganglia). These results provide evidence that 3D mapping of GABA⁺ and Glx using the described methodology provides high reproducibility for application in clinical and neuroscientific studies.     

Spectrum separation resolves partial-volume effect of MRSI as demonstrated on brain tumor scans

Magnetic resonance spectroscopic imaging (MRSI) is currently used clinically in conjunction with anatomical MRI to assess the presence and extent of brain tumors and to evaluate treatment response. Unfortunately, the clinical utility of MRSI is limited by significant variability of in vivo spectra. Spectral profiles show increased variability because of partial coverage of large voxel volumes, infiltration of normal brain tissue by tumors, innate tumor heterogeneity, and measurement noise. We address these problems directly by quantifying the abundance (i.e. volume fraction) within a voxel for each tissue type instead of the conventional estimation of metabolite concentrations from spectral resonance peaks. This 'spectrum separation' method uses the non-negative matrix factorization algorithm, which simultaneously decomposes the observed spectra of multiple voxels into abundance distributions and constituent spectra. The accuracy of the estimated abundances is validated on phantom data. The presented results on 20 clinical cases of brain tumor show reduced cross-subject variability. This is reflected in improved discrimination between high-grade and low-grade gliomas, which demonstrates the physiological relevance of the extracted spectra. These results show that the proposed spectral analysis method can improve the effectiveness of MRSI as a diagnostic tool.     

磁共振谱成像(MRSI)技术的研究进展

磁共振谱成像 (MRSI)在临床诊断中的作用越来越大。目前 ,最有效的快速谱成像法有回波平面法、螺旋轨迹法和阵列采集法。但是 ,这些 MRSI方法的数据采集时间仍然很长 ,速度有待于进一步提高。抑水抑脂脉冲序列基本定型 ,改进的余地不大。在定量的谱分析方面 ,已经实现分析自动化。谱参数估计方法基本完善 ,但在强基线信号时参数估计方法有待于深入研究。目前 ,磁共振谱的图像重建方法局限在 FFT或网格化后的 FFT,这些方法比较简单、快速 ,但也局限了采样脉冲序列 (采样轨迹 )的大胆设计。期望研究出速度更快的 MRSI数据采集脉冲序列。     

Quantitative magnetic resonance spectroscopy at 3T based on the principle of reciprocity

Quantification of magnetic resonance spectroscopy signals using the phantom replacement method requires an adequate correction of differences between the acquisition of the reference signal in the phantom and the measurement in vivo. Applying the principle of reciprocity, sensitivity differences can be corrected at low field strength by measuring the RF transmitter gain needed to obtain a certain flip angle in the measured volume. However, at higher field strength the transmit sensitivity may vary from the reception sensitivity, which leads to wrongly estimated concentrations. To address this issue, a quantification approach based on the principle of reciprocity for use at 3T is proposed and validated thoroughly. In this approach, the RF transmitter gain is determined automatically using a volume‐selective power optimization and complemented with information from relative reception sensitivity maps derived from contrast‐minimized images to correct differences in transmission and reception sensitivity. In this way, a reliable measure of the local sensitivity was obtained. The proposed method is used to derive in vivo concentrations of brain metabolites and tissue water in two studies with different coil sets in a total of 40 healthy volunteers. Resulting molar concentrations are compared with results using internal water referencing (IWR) and Electric REference To access In vivo Concentrations (ERETIC). With the proposed method, changes in coil loading and regional sensitivity due to B₁ inhomogeneities are successfully corrected, as demonstrated in phantom and in vivo measurements. For the tissue water content, coefficients of variation between 2% and 3.5% were obtained (0.6–1.4% in a single subject). The coefficients of variation of the three major metabolites ranged from 3.4–14.5%. In general, the derived concentrations agree well with values estimated with IWR. Hence, the presented method is a valuable alternative for IWR, without the need for additional hardware such as ERETIC and with potential advantages in diseased tissue.     

MRS thermometry calibration at 3 T: effects of protein,ionic concentration and magnetic field strength

MRS thermometry has been utilized to measure temperature changes in the brain, which may aid in the diagnosis of brain trauma and tumours. However, the temperature calibration of the technique has been shown to be sensitive to non‐temperature‐based factors, which may provide unique information on the tissue microenvironment if the mechanisms can be further understood. The focus of this study was to investigate the effects of varied protein content on the calibration of MRS thermometry at 3 T, which has not been thoroughly explored in the literature. The effects of ionic concentration and magnetic field strength were also considered. Temperature reference materials were controlled by water circulation and freezing organic fixed‐point compounds (diphenyl ether and ethylene carbonate) stable to within 0.2 °C. The temperature was measured throughout the scan time with a fluoro‐optic probe, with an uncertainty of 0.16 °C. The probe was calibrated at the National Physical Laboratory (NPL) with traceability to the International Temperature Scale 1990 (ITS‐90). MRS thermometry measures were based on single‐voxel spectroscopy chemical shift differences between water and N‐acetylaspartate (NAA), Δ_(H20‐NAA), using a Philips Achieva 3 T scanner. Six different phantom solutions with varying protein or ionic concentration, simulating potential tissue differences, were investigated within a temperature range of 21–42 °C. Results were compared with a similar study performed at 1.5 T to observe the effect of field strengths. Temperature calibration curves were plotted to convert Δ_(H20‐NAA) to apparent temperature. The apparent temperature changed by ?0.2 °C/% of bovine serum albumin (BSA) and a trend of 0.5 °C/50 mM ionic concentration was observed. Differences in the calibration coefficients for the 10% BSA solution were seen in this study at 3 T compared with a study at 1.5 T. MRS thermometry may be utilized to measure temperature and the tissue microenvironment, which could provide unique unexplored information for brain abnormalities and other pathologies. Copyright © 2015 John Wiley & Sons, Ltd.     

T1 and T2 temperature dependence of female human breast adipose tissue at 1.5 T: groundwork for monitoring thermal therapies in the breast

The T₁ and T₂ temperature dependence of female breast adipose tissue was investigated at 1.5 T in order to evaluate the applicability of relaxation‐based MR thermometry in fat for the monitoring of thermal therapies in the breast. Relaxation times T₁, T₂ and T_2TSE (the apparent T₂ measured using a turbo spin echo readout sequence) were measured in seven fresh adipose breast samples for temperatures from 25 to 65 °C. Spectral water suppression was used to reduce the influence of the residual water signal. The temperature dependence of the relaxation times was characterized. The expected maximum temperature measurement errors based on average calibration lines were calculated. In addition, the heating–cooling reversibility was investigated for two samples. The T₁ and T_2TSE temperature (T) dependence could be fitted well with an exponential function of 1/T. A linear relationship between T₂ and temperature was found. The temperature coefficients (mean ± inter‐sample standard deviation) of T₁ and T_2TSE increased from 25 °C (dT₁/dT = 5.35 ± 0.08 ms/°C, dT_2TSE/dT = 3.82 ± 0.06 ms/°C) to 65 °C (dT₁/dT = 9.50 ± 0.16 ms/°C, dT_2TSE/dT = 7.99 ± 0.38 ms/°C). The temperature coefficient of T₂ was 0.90 ± 0.03 ms/°C. The temperature‐induced changes in the relaxation times were found to be reversible after heating to 65 °C. Given the small inter‐sample variation of the temperature coefficients, relaxation‐based MR thermometry appears to be feasible in breast adipose tissue, and may be used as an adjunct to proton resonance frequency shift (PRFS) thermometry in aqueous tissue (glandular + tumor). Copyright © 2015 John Wiley & Sons, Ltd.     

MRS water resonance frequency in childhood brain tumours: a novel potential biomarker of temperature and tumour environment

¹H MRS thermometry has been investigated for brain trauma and hypothermia monitoring applications but has not been explored in brain tumours. The proton resonance frequency (PRF) of water is dependent on temperature but is also influenced by microenvironment factors, such as fast proton exchange with macromolecules, ionic concentration and magnetic susceptibility. ¹H MRS has been utilized for brain tumour diagnostic and prognostic purposes in children; however, the water PRF measure may provide complementary information to further improve characterization. Water PRF values were investigated from a repository of MRS data acquired from childhood brain tumours and children with apparently normal brains. The cohort consisted of histologically proven glioma (22), medulloblastoma (19) and control groups (28, MRS in both the basal ganglia and parietal white matter regions). All data were acquired at 1.5 T using a short T_E (30 ms) single voxel spectroscopy (PRESS) protocol. Water PRF values were calculated using methyl creatine and total choline. Spectral peak amplitude weighted averaging was used to improve the accuracy of the measurements. Mean PRF values were significantly larger for medulloblastoma compared with glioma, with a difference in the means of 0.0147 ppm (p < 0.05), while the mean PRF for glioma was significantly lower than for the healthy cohort, with a difference in the means of 0.0061 ppm (p < 0.05). This would suggest the apparent temperature of the glioma group was ~1.5 °C higher than the medulloblastomas and ~0.7 °C higher than a healthy brain. However, the PRF shift may not reflect a change in temperature, given that alterations in protein content, microstructure and ionic concentration contribute to PRF shifts. Measurement of these effects could also be used as a supplementary biomarker, and further investigation is required. This study has shown that the water PRF value has the potential to be used for characterizing childhood brain tumours, which has not been reported previously. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

Identification of MRI and 1H MRSI parameters that may predict survival for patients with malignant gliomas

Although MR imaging (MRI) and MR spectroscopic imaging (MRSI) have been applied in the diagnosis and treatment planning for brain tumors, their prognostic significance has not yet been determined. The goal of this study was to identify pre-treatment MRI and MRSI parameters for patients with malignant glioma that may be useful in predicting survival. Two populations of patients with newly-diagnosed malignant glioma were examined with MRI and three-dimensional proton ((1)H) MRSI. Thirty-nine patients (22 grade 3 and 17 glioblastoma multiforme, GBM) were studied prior to surgery, and 33 GBM patients were studied after surgery but prior to treatment with radiation and chemotherapy. Signal intensities of choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), and lactate/lipid (LL) were estimated from the spectra. Recursive partitioning methods were applied to parameters that included age, histological grade, MRI and MRSI variables to generate survival trees. Patients were grouped into high and low risk categories and the corresponding Kaplan-Meier curves were plotted for comparison between groups. The parameters that were selected by recursive partitioning as being predictive of poor outcome were older age, larger contrast enhancement, higher Cho-to-Cr, higher Cho-to-NAA, higher LL and lower Cr-to-NAA abnormalities. The survival functions were significantly different between the sub-groups of patients obtained from the survival tree for both pre-surgery and post-surgery data. The results of this study suggest that pre-treatment MRI and three-dimensional (1)H-MRSI provide information that predicts outcome for patients with malignant gliomas and have drawn attention to variables that should be examined prospectively in future studies using these techniques.     

Reproducibility of whole‐brain temperature mapping and metabolite quantification using proton magnetic resonance spectroscopy

Assessing brain temperature can provide important information about disease processes (e.g., stroke, trauma) and therapeutic effects (e.g., cerebral hypothermia treatment). Whole‐brain magnetic resonance spectroscopic imaging (WB‐MRSI) is increasingly used to quantify brain metabolites across the entire brain. However, its feasibility and reliability for estimating brain temperature needs further validation. Therefore, the present study evaluates the reproducibility of WB‐MRSI for temperature mapping as well as metabolite quantification across the whole brain in healthy volunteers. Ten healthy adults were scanned on three occasions 1 week apart. Brain temperature, along with four commonly assessed brain metabolites—total N‐acetyl‐aspartate (tNAA), total creatine (tCr), total choline (tCho) and myo‐inositol (mI)—were measured from WB‐MRSI data. Reproducibility was evaluated using the coefficient of variation (CV). The measured mean (range) of the intra‐subject CVs was 0.9% (0.6%‐1.6%) for brain temperature mapping, and 4.7% (2.5%‐15.7%), 6.4% (2.4%‐18.9%) and 14.2% (4.4%‐52.6%) for tNAA, tCho and mI, respectively, with reference to tCr. Consistently larger variability was found when using H₂O as the reference for metabolite quantifications: 7.8% (3.3%‐17.8%), 7.8% (3.1%‐18.0%), 9.8% (3.7%‐31.0%) and 17.0% (5.9%‐54.0%) for tNAA, tCr, tCho and mI, respectively. Further, the larger the brain region (indicated by a greater number of voxels within that region), the better the reproducibility for both temperature and metabolite estimates. Our results demonstrate good reproducibility of whole‐brain temperature and metabolite measurements using the WB‐MRSI technique.     

Global brain metabolic quantification with whole‐head proton MRS at 3 T

Total N‐acetyl‐aspartate + N‐acetyl‐aspartate–glutamate (NAA), total creatine (Cr) and total choline (Cho) proton MRS (¹H–MRS) signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%–65% of the brain. Here we wish to demonstrate that non‐localized, whole‐head (WH) ¹H–MRS captures just the brain's contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end, 27 young healthy adults (18 men, 9 women), 29.9 ± 8.5 years old, were recruited and underwent T₁‐weighted MRI for tissue segmentation, non‐localizing, approximately 3 min WH ¹H–MRS (T_E/T_R/T_I = 5/10 1 /940 ms) and 30 min ¹H–MR spectroscopic imaging (MRSI) (T_E/T_R = 35/2100 ms) in a 360 cm³ volume of interest (VOI) at the brain's center. The VOI absolute NAA, Cr and Cho concentrations, 7.7 ± 0.5, 5.5 ± 0.4 and 1.3 ± 0.2 mM, were all within 10% of the WH: 8.6 ± 1.1, 6.0 ± 1.0 and 1.3 ± 0.2 mM. The mean NAA/Cr and NAA/Cho ratios in the WH were only slightly higher than the “brain‐only” VOI: 1.5 versus 1.4 (7%) and 6.6 versus 5.9 (11%); Cho/Cr were not different. The brain/WH volume ratio was 0.31 ± 0.03 (brain ≈ 30% of WH volume). Air‐tissue susceptibility‐driven local magnetic field changes going from the brain outwards showed sharp gradients of more than 100 Hz/cm (1 ppm/cm), explaining the skull's Cr and Cho signal losses through resonance shifts, line broadening and destructive interference. The similarity of non‐localized WH and localized VOI NAA, Cr and Cho concentrations and their ratios suggests that their signals originate predominantly from the brain. Therefore, the fast, comprehensive WH‐¹H‐MRS method may facilitate quantification of these metabolites, which are common surrogate markers in neurological disorders.     

Age-dependent brain temperature decline assessed by diffusion-weighted imaging thermometry

Brain metabolism declines with age, but cerebral blood flow (CBF) is less age dependent. We therefore hypothesized that the brain temperature would decline with age, and measured the temperatures of the lateral ventricles in healthy volunteers. Diffusion‐weighted imaging (DWI) data from 45 healthy volunteers [mean (± standard deviation) age, 30.6 ± 8.66 years; range, 19–56 years] were used for this study. The temperature of water molecules is directly related to the diffusion coefficient, so that the temperature of cerebrospinal fluid can be measured using DWI. Temperature was calculated using the equation, T ( °C) = 2256.74/ln(4.39221/D) – 273.15, where D is the diffusion coefficient. The lateral ventricles were manually extracted by an experienced neuroradiologist on b₀ images. The mean ventricular temperature was determined from the distribution function of the temperature of all selected voxels. The mean lateral ventricular temperature in healthy volunteers showed a linear decrease with age (correlation coefficient R² = 0.8879; p < 0.01), presumably caused by an asynchronous decline in brain metabolism and CBF. DWI‐based thermometry demonstrates that ventricular temperature declines with the normal aging process. Further study is warranted to define the relationships between temperature, metabolism and circulation. Copyright © 2011 John Wiley & Sons, Ltd.     

Reproducibility of serial whole‐brain MR Spectroscopic Imaging

The reproducibility of serial measurements using a volumetric proton MR Spectroscopic Imaging (MRSI) acquisition implemented at 3 Tesla and with lipid suppression by inversion‐recovery has been evaluated. Data were acquired from two subjects at five time points, and processed using fully‐automated procedures that included rigid registration between studies. These data were analyzed to determine coefficients of variance (COV) for each metabolite and for metabolite ratio images based on an individual voxel analysis, as well as for average and grey‐matter and white‐matter values from atlas‐defined brain regions. The volumetric MRSI acquisition was found to obtain data of sufficient quality for analysis over 70 ± 6% of the total brain volume, and spatial distributions of the resultant COV values were found to reflect the known distributions of susceptibility‐induced magnetic field inhomogeneity. Median values of the resultant voxel‐based COVs were 6.2%, 7.2%, and 9.7% for N–acetylaspartate, creatine, and choline respectively. The corresponding mean values obtained following averaging over lobar‐scale brain regions within the cerebrum were 3.5%, 3.7%, and 5.2%. These results indicate that longitudinal volumetric MRSI studies with post‐acquisition registration can provide an intra‐subject reproducibility for voxel‐based analyses that is comparable to previously‐reported single‐voxel MRS measurements, while additionally enabling increased sensitivity by averaging over larger tissue volumes. Copyright © 2009 John Wiley & Sons, Ltd.     

Validation of fast MR thermometry at 1.5 T with gradient-echo echo planar imaging sequences: phantom and clinical feasibility studies

The purpose of this work was to validate in phantom studies and demonstrate the clinical feasibility of MR proton resonance frequency thermometry at 1.5 T with segmented gradient-echo echo planar imaging (GRE-EPI) sequences during liver tumour radiofrequency (RF) ablation. Classical GRE acquisitions and segmented GRE-EPI acquisitions were performed at 1.5 T during simultaneous RF heating with an MR-compatible RF electrode placed in an agar gel phantom. Temperature increments were calculated and compared with four optical temperature probe measurements using Bland- Altman analysis. In a preliminary clinical feasibility study, the rapid GRE-EPI sequence (echo train length = 13) was used for MR temperature monitoring of RF ablation of liver tumours in three patient procedures. For phantom experiments, the Bland-Altman mean of differences between MR and optical probe temperature measurements was <0.4 degrees C, and the 95% limits of agreement value was <1.4 degrees C. For the in vivo studies, respiratory-triggered GRE-EPI acquisitions yielded a temperature accuracy of 1.3 +/- 0.4 degrees C (acquisition time = 0.6 s/image, spatial coverage of three slices/respiratory cycle). MR proton resonance frequency thermometry at 1.5 T yields precise and accurate measurements of temperature increment with both classical GRE and rapid GRE-EPI sequences. Rapid GRE-EPI sequences minimize intra-scan motion effects and can be used for MR thermometry during RF ablation in moving organs. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Quantitative T2* imaging of metastatic human breast cancer to brain in the nude rat at 3 T

This study uses quantitative T₂* imaging to track ferumoxides–protamine sulfate (FEPro)‐labeled MDA‐MB‐231BR‐Luc (231BRL) human breast cancer cells that metastasize to the nude rat brain. Four cohorts of nude rats were injected intracardially with FEPro‐labeled, unlabeled or tumor necrosis factor‐related apoptosis‐inducing ligand(TRAIL)‐treated (to induce apoptosis) 231BRL cells, or saline, in order to develop metastatic breast cancer in the brain. The heads of the rats were imaged serially over 3–4 weeks using gradient multi‐echo and turbo spin‐echo pulse sequences at 3 T with a solenoid receive‐only 4‐cm‐diameter coil. Quantitative T₂* maps of the whole brain were obtained by the application of single‐exponential fitting to the signal intensity of T₂* images, and the distribution of T₂* values in brain voxels was calculated. MRI findings were correlated with Prussian blue staining and immunohistochemical staining for iron in breast cancer and macrophages. Quantitative analysis of T₂* from brain voxels demonstrated a significant shift to lower values following the intracardiac injection of FEPro‐labeled 231BRL cells, relative to animals receiving unlabeled cells, apoptotic cells or saline. Quartile analysis based on the T₂* distribution obtained from brain voxels demonstrated significant differences (p < 0.0083) in the number of voxels with T₂* values in the ranges 10–35 ms (Q1), 36–60 ms (Q2) and 61–86 ms (Q3) from 1 day to 3 weeks post‐infusion of labeled 231BRL cells, compared with baseline scans. There were no significant differences in the distribution of T₂* obtained from serial MRI in rats receiving unlabeled or TRAIL‐treated cells or saline. Histologic analysis demonstrated isolated Prussian blue‐positive breast cancer cells scattered in the brains of rats receiving labeled cells, relative to animals receiving unlabeled or apoptotic cells. Quantitative T₂* analysis of FEPro‐labeled metastasized cancer cells was possible even after the hypointense voxels were no longer visible on T₂*‐weighted images. Published in 2010 by John Wiley & Sons, Ltd.     

Multiparametric human hepatocellular carcinoma characterization and therapy response evaluation by hyperpolarized 13C MRSI

Individual tumor characterization and treatment response monitoring based on current medical imaging methods remain challenging. This work investigates hyperpolarized ¹³ C compounds in an orthotopic rat hepatocellular carcinoma (HCC) model system before and after transcatheter arterial embolization (TAE). HCC ranks amongst the top six most common cancer types in humans and accounts for one‐third of cancer‐related deaths worldwide. Early therapy response monitoring could aid in the development of personalized therapy approaches and novel therapeutic concepts. Measurements with selectively ¹³ C ‐labeled and hyperpolarized urea, pyruvate and fumarate were performed in tumor‐bearing rats before and after TAE. Two‐dimensional, slice‐selective MRSI was used to obtain spatially resolved maps of tumor perfusion, cell energy metabolic conversion rates and necrosis, which were additionally correlated with immunohistochemistry. All three injected compounds, taken together with their respective metabolites, exhibited similar signal distributions. TAE induced a decrease in blood flow into the tumor and thus a decrease in tumor to muscle and tumor to liver ratios of urea, pyruvate and its metabolites, alanine and lactate, whereas conversion rates remained stable or increased on TAE in tumor, muscle and liver tissue. Conversion from fumarate to malate successfully indicated individual levels of necrosis, and global malate signals after TAE suggested the washout of fumarase or malate itself on necrosis. This study presents a combination of three ¹³ C compounds as novel candidate biomarkers for a comprehensive characterization of genetically and molecularly diverse HCC using hyperpolarized MRSI, enabling the simultaneous detection of differences in tumor perfusion, metabolism and necrosis. If, as in this study, bolus dynamics are not required and qualitative perfusion information is sufficient, the desired information could be extracted from hyperpolarized fumarate and pyruvate alone, acquired at higher fields with better spectral separation. Copyright © 2016 John Wiley & Sons, Ltd.     

Towards optimized MR thermometry of the human heart at 3T

Catheter ablation using radio frequency (RF) has been used increasingly for the treatment of cardiac arrhythmias and may be combined with proton resonance frequency shift (PRFS) ?based MR thermometry to determine the therapy endpoint. We evaluated the suitability of two different MR thermometry sequences (TFE and TFE‐EPI) and three blood suppression techniques. Experiments were performed without heating, using an optimized imaging protocol including navigator respiratory compensation, cardiac triggering, and image processing for the compensation of motion and susceptibility artefacts. Blood suppression performance and its effect on temperature stability were evaluated in the ventricular septum of eight healthy volunteers using multislice double inversion recovery (MDIR), motion sensitized driven equilibrium (MSDE), and inflow saturation by saturation slabs (IS). It was shown that blood suppression during MR thermometry improves the contrast‐to‐noise ratio (CNR), the robustness of the applied motion correction algorithm as well as the temperature stability. A gradient echo sequence accelerated by an EPI readout and parallel imaging (SENSE) and using inflow saturation blood suppression was shown to achieve the best results. Temperature stabilities of 2 °C or better in the ventricular septum with a spatial resolution of 3.5 × 3.5 × 8mm³ and a temporal resolution corresponding to the heart rate of the volunteer, were observed. Our results indicate that blood suppression improves the temperature stability when performing cardiac MR thermometry. The proposed MR thermometry protocol, which optimizes temperature stability in the ventricular septum, represents a step towards PRFS‐based MR thermometry of the heart at 3 T. Copyright © 2011 John Wiley & Sons, Ltd.