Multi‐parametric MRI characterization of healthy human thigh muscles at 3.0 T – relaxation,magnetization transfer,fat/water,and diffusion tensor imaging

Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo‐pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin‐echo T₂ imaging (with and without fat signal suppression, FS), selective inversion recovery for T₁ and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re‐imaged an average of 35 days later. Pre‐testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between‐day intra‐class correlations were observed in all quantitative indices except for the macromolecular‐to‐free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two‐way analysis of variance revealed no significant between‐day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland–Altman plots, and low repeatability coefficients were obtained for all parameters. Among‐muscle differences in the quantitative MRI indices and inter‐class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T₁, T₂, fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters. Copyright © 2014 John Wiley & Sons, Ltd.     

Characterization of a rat orthotopic pancreatic head tumor model using three‐dimensional and quantitative multi‐parametric MRI

The purpose of this study was to investigate the reliability of 3D isotropic MRI and quantitative multi‐parametric MRI characterization on an orthotopic pancreatic head tumor model in rats. 3D isotropic T₂‐weighted MRI was performed as a routine for tumor longitudinal follow‐up and volume estimation. Common bile duct diameter was measured from 3D multiplanar reconstruction. Quantitative multi‐parametric measurements including pixel‐wise T₂, T₁ relaxivity, apparent diffusion coefficient (ADC) and apparent diffusion kurtosis mapping were performed twice throughout tumor growth. Semi‐quantitative and quantitative analyses based on an extended Tofts model were applied to region‐of‐interest‐based dynamic contrast‐enhanced imaging, followed by contrast ratio measurement on standard contrast‐enhanced imaging. Moreover, low‐level texture‐based analysis was inspected for T₂, T₁, ADC and contrast ratio measurements. Results indicated that multi‐parametric MRI showed good reproducibility for tumor characterization; the measurements were not affected by tumor growth. Tumor growth was further confirmed with histology examinations. To conclude, state‐of‐the‐art clinical MRI techniques were translated to this preclinical tumor model with high reliability, and have paved the way for translational oncology studies on this tumor model.     

Quantitative magnetization transfer imaging of rodent glioma using selective inversion recovery

Magnetization transfer (MT) provides an indirect means to detect noninvasively variations in macromolecular contents in biological tissues, but, so far, there have been only a few quantitative MT (qMT) studies reported in cancer, all of which used off‐resonance pulsed saturation methods. This article describes the first implementation of a different qMT approach, selective inversion recovery (SIR), for the characterization of tumor in vivo using a rodent glioma model. The SIR method is an on‐resonance method capable of fitting qMT parameters and T₁ relaxation time simultaneously without mapping B₀ and B₁, which is very suitable for high‐field qMT measurements because of the lower saturation absorption rate. The results show that the average pool size ratio (PSR, the macromolecular pool versus the free water pool) in rat 9 L glioma (5.7%) is significantly lower than that in normal rat gray matter (9.2%) and white matter (17.4%), which suggests that PSR is potentially a sensitive imaging biomarker for the assessment of brain tumor. Despite being less robust, the estimated MT exchange rates also show clear differences from normal tissues (19.7 Hz for tumors versus 14.8 and 10.2 Hz for gray and white mater, respectively). In addition, the influence of confounding effects, e.g. B₁ inhomogeneity, on qMT parameter estimates is investigated with numerical simulations. These findings not only help to better understand the changes in the macromolecular contents of tumors, but are also important for the interpretation of other imaging contrasts, such as chemical exchange saturation transfer of tumors. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B‐cell lymphoma – a whole‐body MRI and diffusion‐weighted imaging study

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B‐cell lymphoma (DLBCL), 18 patients with histology‐confirmed DLBCL underwent 3‐T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T₁‐weighted pre‐ and post‐contrast, T₂‐weighted with and without fat suppression, and a single‐shot echo‐planar diffusion‐weighted imaging (DWI) with two b values (0 and 800 s/mm²). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T₂‐weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T₂‐weighted image with fat suppression decreased significantly (p < 0.01), and that of the T₁‐weighted pre‐contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10^–3 mm²/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = ?0.62, p < 0.01). In conclusion, this study indicates that T₂‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI. Copyright © 2013 John Wiley & Sons, Ltd.     

Rapid simultaneous acquisition of T1 and T2 mapping images using multishot double spin‐echo EPI and automated variations of TR and TE (ms‐DSEPI‐T12)

A rapid method of simultaneous T₁ and T₂ measurement is presented which uses a segmented echo‐planar readout with varying repetition times (TR) and echo times (TE). This method is useful in T₁ mapping for analysis of dynamic contrast enhanced MRI (DCE‐MRI), where T₁ can be used to estimate contrast agent concentration. In the application of this method to dynamic imaging, the equilibrium magnetization is measured on pre‐contrast images and incorporated into post‐contrast T₁ calculations for improved accuracy. Simultaneous T₂ measurement allows correction of T₂ effects in the T₁ map which may occur at high contrast agent concentrations, and is performed without significant imaging time penalty. Phantom and in vivo results show the usefulness of this technique for analysis of contrast enhancement kinetics. Accurate rapid contrast agent concentration measurement may be useful for analyzing the distribution and kinetics of contrast agents or labeled pharmaceuticals. Copyright © 2009 John Wiley & Sons, Ltd.     

DCE and DW-MRI monitoring of vascular disruption following VEGF-Trap treatment of a rat glioma model

Vascular‐targeted therapies have shown promise as adjuvant cancer treatment. As these agents undergo clinical evaluation, sensitive imaging biomarkers are needed to assess drug target interaction and treatment response. In this study, dynamic contrast enhanced MRI (DCE‐MRI) and diffusion‐weighted MRI (DW‐MRI) were evaluated for detecting response of intracerebral 9 L gliosarcomas to the antivascular agent VEGF‐Trap, a fusion protein designed to bind all forms of Vascular Endothelial Growth Factor‐A (VEGF‐A) and Placental Growth Factor (PGF). Rats with 9 L tumors were treated twice weekly for two weeks with vehicle or VEGF‐Trap. DCE‐ and DW‐MRI were performed one day prior to treatment initiation and one day following each administered dose. Kinetic parameters (K^trans, volume transfer constant; k_ep, efflux rate constant from extravascular/extracellular space to plasma; and v_p, blood plasma volume fraction) and the apparent diffusion coefficient (ADC) over the tumor volumes were compared between groups. A significant decrease in kinetic parameters was observed 24 hours following the first dose of VEGF‐Trap in treated versus control animals (p < 0.05) and was accompanied by a decline in ADC values. In addition to the significant hemodynamic effect, VEGF‐Trap treated animals exhibited significantly longer tumor doubling times (p < 0.05) compared to the controls. Histological findings were found to support imaging response metrics. In conclusion, kinetic MRI parameters and change in ADC have been found to serve as sensitive and early biomarkers of VEGF‐Trap anti‐vascular targeted therapy. Copyright © 2011 John Wiley & Sons, Ltd.     

Classification of prostatic diseases by means of multivariate analysis on in vivo proton MRSI and DCE‐MRI data

Multivariate analysis has been applied on proton magnetic resonance spectroscopic imaging (¹H‐MRSI) and dynamic contrast enhanced MRI (DCE‐MRI) data of patients with different prostatic diseases such as chronic inflammation, fibrosis and adenocarcinoma. Multivariate analysis offers a global view of the entire range of information coming from both the imaging and spectroscopic side of NMR technology, leading to an integrated picture of the system relying upon the entire metabolic and dynamic profile of the studied samples. In this study, we show how this approach, applied to ¹H‐MRSI/DCE‐MRI results, allows us to differentiate among the various prostatic diseases in a non‐invasive way with a 100% accuracy. These findings suggest that multivariate analysis of ¹H‐MRSI/DCE‐MRI can significantly improve the diagnostic accuracy for these pathological entities. From a more theoretical point of view, the complementation of a single biomarker approach with an integrated picture of the entire metabolic and dynamic profile allows for a more realistic appreciation of pathological entities. Copyright © 2009 John Wiley & Sons, Ltd.     

Early detection of human glioma sphere xenografts in mouse brain using diffusion MRI at 14.1 T

Glioma models have provided important insights into human brain cancers. Among the investigative tools, MRI has allowed their characterization and diagnosis. In this study, we investigated whether diffusion MRI might be a useful technique for early detection and characterization of slow‐growing and diffuse infiltrative gliomas, such as the proposed new models, LN‐2669GS and LN‐2540GS glioma sphere xenografts. Tumours grown in these models are not visible in conventional T₂‐weighted or contrast‐enhanced T₁‐weighted MRI at 14.1 T. Diffusion‐weighted imaging and diffusion tensor imaging protocols were optimized for contrast by exploring long diffusion times sensitive for probing the microstructural alterations induced in the normal brain by the slow infiltration of glioma sphere cells. Compared with T₂‐weighted images, tumours were properly identified in their early stage of growth using diffusion MRI, and confirmed by localized proton MR spectroscopy as well as immunohistochemistry. The first evidence of tumour presence was revealed for both glioma sphere xenograft models three months after tumour implantation, while no necrosis, oedema or haemorrhage were detected either by MRI or by histology. Moreover, different values of diffusion indices, such as mean diffusivity and fractional anisotropy, were obtained in tumours grown from LN‐2669GS and LN‐2540GS glioma sphere lines. These observations highlighted diverse tumour microstructures for both xenograft models, which were reflected in histology. This study demonstrates the ability of diffusion MRI techniques to identify and investigate early stages of slow‐growing, invasive tumours in the mouse brain, thus providing a potential imaging biomarker for early detection of tumours in humans.     

Assessment of the need for DCE MRI in the detection of dominant lesions in the whole gland: Correlation between histology and MRI of prostate cancer

The purpose of this study was to evaluate the utility of dynamic contrast‐enhanced magnetic resonance imaging (DCE MRI) in the detection of dominant prostate tumors with multi‐parametric MRI of the whole gland. Combined diffusion tensor imaging (DTI) and DCE MRI from 16 patients with biopsy‐proven prostate cancer and no previous treatment were acquired with a 3.0‐T MRI scanner prior to radical prostatectomy, and used to identify dominant tumors. MRI results were validated by whole‐mount histology. Paired t‐test and Wilcoxon test, logistic generalized linear mixed effect models and receiver operating characteristic (ROC) analyses were used for the estimation of the statistical significance of the results. In the peripheral zone (PZ), the areas under the ROC curve (ROC‐AUC) were 0.98 (sensitivity, 96%; specificity, 98%) for DTI, 0.96 (sensitivity, 92%; specificity, 97%) for DCE and 0.99 (sensitivity, 98%; specificity, 98%) for DTI + DCE. In the entire prostate, the ROC‐AUC values were 0.96 (sensitivity, 84%; specificity, 95%) for DTI, 0.87 (sensitivity, 45%; specificity, 94%) for DCE and 0.96 (sensitivity, 88%; specificity, 98%) for DTI + DCE. The increase in ROC‐AUC by the addition of DCE was not statistically significant in either PZ or the entire prostate. The results of this study have shown that DTI identified dominant tumors with high accuracy in both PZ and the entire prostate, whereas the inclusion of DCE MRI had no significant impact on the identification of either PZ or entire prostate dominant lesions. Our results suggest that the inclusion of DCE MRI may not increase the accuracy of dominant lesion detection, allowing for faster, better tolerated imaging studies.     

Relationship between diffusion parameters derived from intravoxel incoherent motion MRI and perfusion measured by dynamic contrast‐enhanced MRI of soft tissue tumors

Our aim was to evaluate the link between diffusion parameters measured by intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI) and the perfusion metrics obtained with dynamic contrast‐enhanced (DCE) MRI in soft tissue tumors (STTs). Twenty‐eight patients affected by histopathologically confirmed STT were included in a prospective study. All patients underwent both DCE MRI and IVIM DWI. The perfusion fraction f, diffusion coefficient D and perfusion‐related diffusion coefficient D* were estimated using a bi‐exponential function to fit the DWI data. DCE MRI was acquired with a temporal resolution of 3–5 s. Maps of the initial area under the gadolinium concentration curve (IAUGC), time to peak (TTP) and maximum slope of increase (MSI) were derived using commercial software. The relationships between the DCE MRI and IVIM DWI measurements were assessed by Spearman's test. To exclude false positive results under multiple testing, the false discovery rate (FDR) procedure was applied. The Mann–Whitney test was used to evaluate the differences between all variables in patients with non‐myxoid and myxoid STT. No significant relationship was found between IVIM parameters and any DCE MRI parameters. Higher f and D*f values were found in non‐myxoid tumors compared with myxoid tumors (p = 0.004 and p = 0.003, respectively). MSI was significantly higher in non‐myxoid tumors than in myxoid tumors (p = 0.029). From the visual assessments of single clinical cases, both f and D*f maps were in satisfactory agreement with DCE maps in the extreme cases of an avascular mass and a highly vascularized mass, whereas, for tumors with slight vascularity or with a highly heterogeneous perfusion pattern, this association was not straightforward. Although IVIM DWI was demonstrated to be feasible in STT, our data did not support evident relationships between perfusion‐related IVIM parameters and perfusion measured by DCE MRI. Copyright © 2015 John Wiley & Sons, Ltd.     

Diffusion tensor imaging MRI of sickle cell kidney disease: initial results and comparison with iron deposition

Chronic kidney disease (CKD) occurs in over one‐third of patients with sickle cell disease (SCD) and can progress to end‐stage renal disease. Unfortunately, current clinical assessments of kidney function are insensitive to early‐stage CKD. Previous studies have shown that diffusion magnetic resonance imaging (MRI) can sensitively detect regional renal microstructural changes associated with early‐stage CKD. However, previous MRI studies in patients with SCD have been largely limited to the detection of renal iron deposition assessed by T₂* relaxometry. In this pilot imaging study, we compare MRI assessments of renal microstructure (diffusion) and iron deposition (T₂*) in patients with SCD and in non‐SCD control subjects. Diffusion tensor imaging (DTI) and T₂* relaxometry MRI data were obtained for pediatric (n = 5) and adult (n = 4) patients with SCD, as well as for non‐SCD control subjects (n = 10), on a Siemens Espree 1.5‐T MRI scanner. A region‐of‐interest analysis was used to calculate mean medullary and cortical values for each MRI metric. MRI findings were also compared with clinical assessments of renal function and hemolysis. Patients with SCD showed a significant decrease in medullary fractional anisotropy (FA, p = 0.0001) in comparison with non‐SCD subjects, indicative of microstructural alterations in the renal medulla of patients with SCD. Cortical and medullary reductions in T₂* (increased iron deposition, p = ≤0.0001) were also observed. Significant correlations were also observed between kidney T₂* assessments and multiple measures of hemolysis. This is the first DTI MRI study of patients with SCD to demonstrate reductions in medullary FA despite no overt CKD [estimated glomerular filtration rate (eGFR) > 100 mL/min/1.73 m²]. These medullary FA changes are consistent with previous studies in patients with CKD, and suggest that DTI MRI can provide a useful measure of kidney injury to complement MRI assessments of iron deposition.     

The MT pool size ratio and the DTI radial diffusivity may reflect the myelination in shiverer and control mice

A quantitative magnetization transfer (qMT) technique was employed to quantify the ratio of the sizes of the bound and free water proton pools in ex vivo mouse brains. The goal was to determine the pool size ratio sensitivity to myelin. Fixed brains from both shiverer mice and control littermates were imaged. The pool size ratio in the corpus callosum of shiverer mice was substantially lower than that in the control mice, while there was no distinguishable difference in the pool size ratio in the gray matter. These results correlate with diffusion tensor imaging (DTI) derived radial diffusivity which previously was shown to reflect myelin integrity in this animal model. Histological study reveals the presence of myelin in control mice white matter and the absence of myelin in shiverer mice white matter, supporting the qMT and DTI results. Our findings support the view that qMT may be used for estimating myelin integrity. Copyright © 2008 John Wiley & Sons, Ltd.     

High‐field (11.75T) multimodal MR imaging of exercising hindlimb mouse muscles using a non‐invasive combined stimulation and force measurement device

We have designed and constructed an experimental set‐up allowing electrical stimulation of hindlimb mouse muscles and the corresponding force measurements at high‐field (11.75T). We performed high‐resolution multimodal MRI (including T₂‐weighted imaging, angiography and diffusion) and analysed the corresponding MRI changes in response to a stimulation protocol. Mice were tested twice over a 1‐week period to investigate the reliability of mechanical measurements and T₂ changes associated with the stimulation protocol. Additionally, angiographic images were obtained before and immediately after the stimulation protocol. Finally, multislice diffusion imaging was performed before, during and immediately after the stimulation session. Apparent diffusion coefficient (ADC) maps were calculated on the basis of diffusion weighted images (DWI). Both force production and T₂ values were highly reproducible as illustrated by the low coefficient of variation (<8%) and high intraclass correlation coefficient (≥0.75) values. Maximum intensity projection angiographic images clearly showed a strong vascular effect resulting from the stimulation protocol. Although a motion sensitive imaging sequence was used (echo planar imaging) and in spite of the strong muscle contractions, motion artifacts were minimal for DWI recorded under exercising conditions, thereby underlining the robustness of the measurements. Mean ADC values increased under exercising conditions and were higher during the recovery period as compared with the corresponding control values. The proposed experimental approach demonstrates accurate high‐field multimodal MRI muscle investigations at a preclinical level which is of interest for monitoring the severity and/or the progression of neuromuscular diseases but also for assessing the efficacy of potential therapeutic interventions. Copyright © 2014 John Wiley & Sons, Ltd.     

Comparing diagnostic accuracy of luminal water imaging with diffusion‐weighted and dynamic contrast‐enhanced MRI in prostate cancer: A quantitative MRI study

Luminal water imaging (LWI) is a new MRI T₂ mapping technique that has been developed with the aim of diagnosis of prostate carcinoma (PCa). This technique measures the fractional amount of luminal water in prostate tissue, and has shown promising preliminary results in detection of PCa. To include LWI in clinical settings, further investigation on the accuracy of this technique is required. In this study, we compare the diagnostic accuracy of LWI with those of diffusion‐weighted imaging (DWI) and dynamic contrast‐enhanced (DCE) MRI in detection and grading of PCa. Fifteen patients with biopsy‐proven PCa consented to participate in this ethics‐board‐approved prospective study. Patients were examined with LWI, DWI, and DCE sequences at 3 T prior to radical prostatectomy. Maps of MRI parameters were generated and registered to whole‐mount histology. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of individual and combined MR parameters. Correlation with Gleason score (GS) was evaluated using Spearman's rank correlation test. The results show that area under the ROC curve (AUC) obtained from LWI was equal to or higher than the AUC obtained from DWI, DCE, or their combination, in peripheral zone (0.98 versus 0.90, 0.89, and 0.91 respectively), transition zone (0.99 versus 0.98, n/a, and 0.98), and the entire prostate (0.85 versus 0.81, 0.75, and 0.84). The strongest correlation with GS was achieved from LWI (ρ = ?0.81 ± 0.09, P < 0.001). Results of this pilot study show that LWI performs equally well as, or better than, DWI and DCE in detection of PCa. LWI provides significantly higher correlation with GS than DWI and DCE. This technique can potentially be included in clinical MRI protocols to improve characterization of tumors. However, considering the small size of the patient population in this study, a further study with a larger cohort of patients and broader range of GS is required to confirm the findings and draw a firm conclusion on the applicability of LWI in clinical settings.     

Dynamic contrast‐enhanced MRI in mouse tumors at 11.7 T: comparison of three contrast agents with different molecular weights to assess the early effects of combretastatin A4

Dynamic contrast‐enhanced (DCE)‐MRI is useful to assess the early effects of drugs acting on tumor vasculature, namely anti‐angiogenic and vascular disrupting agents. Ultra‐high‐field MRI allows higher‐resolution scanning for DCE‐MRI while maintaining an adequate signal‐to‐noise ratio. However, increases in susceptibility effects, combined with decreases in longitudinal relaxivity of gadolinium‐based contrast agents (GdCAs), make DCE‐MRI more challenging at high field. The aim of this work was to explore the feasibility of using DCE‐MRI at 11.7 T to assess the tumor hemodynamics of mice. Three GdCAs possessing different molecular weights (gadoterate: 560 Da, 0.29 mmol Gd/kg; p846: 3.5 kDa, 0.10 mmol Gd/kg; and p792: 6.47 kDa, 0.15 mmol Gd/kg) were compared to see the influence of the molecular weight in the highlight of the biologic effects induced by combretastatin A4 (CA4). Mice bearing transplantable liver tumor (TLT) hepatocarcinoma were divided into two groups (n = 5–6 per group and per GdCA): a treated group receiving 100 mg/kg CA4, and a control group receiving vehicle. The mice were imaged at 11.7 T with a T₁‐weighted FLASH sequence 2 h after the treatment. Individual arterial input functions (AIFs) were computed using phase imaging. These AIFs were used in the Extended Tofts Model to determine K^trans and v_p values. A separate immunohistochemistry study was performed to assess the vascular perfusion and the vascular density. Phase imaging was used successfully to measure the AIF for the three GdCAs. In control groups, an inverse relationship between the molecular weight of the GdCA and K^trans and v_p values was observed. K^trans was significantly decreased in the treated group compared with the control group for each GdCA. DCE‐MRI at 11.7 T is feasible to assess tumor hemodynamics in mice. With K^trans, the three GdCAs were able to track the early vascular effects induced by CA4 treatment. Copyright © 2014 John Wiley & Sons, Ltd.     

Multiparametric MRI analysis for the evaluation of MR‐guided high intensity focused ultrasound tumor treatment

For the clinical application of high intensity focused ultrasound (HIFU) for thermal ablation of malignant tumors, accurate treatment evaluation is of key importance. In this study, we have employed a multiparametric MRI protocol, consisting of quantitative T₁, T₂, ADC, amide proton transfer (APT), T_1ρ and DCE‐MRI measurements, to evaluate MR‐guided HIFU treatment of subcutaneous tumors in rats. K‐means clustering using all different combinations of the endogenous contrast MRI parameters (feature vectors) was performed to segment the multiparametric data into tissue populations with similar MR parameter values. The optimal feature vector for identification of the extent of non‐viable tumor tissue after HIFU treatment was determined by quantitative comparison between clustering‐derived and histology‐derived non‐viable tumor fractions. The highest one‐to‐one correspondence between these clustering‐based and histology‐based non‐viable tumor fractions was observed for the feature vector {ADC, APT‐weighted signal} (R² to line of identity (R²_y=x) = 0.92) and the strongest agreement was seen 3 days after HIFU (R²_y=x = 0.97). To compare the multiparametric MRI analysis results with conventional HIFU monitoring and evaluation methods, the histology‐derived non‐viable tumor fractions were also quantitatively compared with non‐perfused tumor fractions (derived from the level of contrast enhancement in the DCE‐MRI measurements) and 240 CEM tumor fractions (i.e. thermal dose > 240 cumulative equivalent minutes at 43 °C). The correlation between histology‐derived non‐viable tumor fractions directly after HIFU and the 240 CEM fractions was high, but not significant. The non‐perfused fractions overestimated the extent of non‐viable tumor tissue directly after HIFU, whereas an underestimation was observed 3 days after HIFU. In conclusion, we have shown that a multiparametric MR analysis, especially based on the ADC and the APT‐weighted signal, can potentially be used to determine the extent of non‐viable tumor tissue 3 days after HIFU treatment. We expect that this method can be incorporated in the current clinical workflow of MR–HIFU ablation therapies. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantitative MRI in murine radiation‐induced rectocolitis: comparison with histopathological inflammation score

Murine radiation‐induced rectocolitis is considered to be a relevant animal model of gastrointestinal inflammation. The purpose of our study was to compare quantitative MRI and histopathological features in this gastrointestinal inflammation model. Radiation rectocolitis was induced by localized single‐dose radiation (27 Gy) in Sprague‐Dawley rats. T₂‐weighted, T₁‐weighted and diffusion‐weighted MRI was performed at 7 T in 16 rats between 2 and 4 weeks after irradiation and in 10 control rats. Rats were sacrificed and the histopathological inflammation score of the colorectal samples was assessed. The irradiated rats showed significant increase in colorectal wall thickness (2.1 ± 0.3 mm versus 0.8 ± 0.3 mm in control rats, P < 0.0001), normalized T₂ signal intensity (4 ± 0.8 versus 2 ± 0.4 AU, P < 0.0001), normalized T₁ signal intensity (1.4 ± 0.1 versus 1.1 ± 0.2 AU, P = 0.0009) and apparent and pure diffusion coefficients (ADC and D) (2.06 × 10^?3 ± 0.34 versus 1.51 × 10^?3 ± 0.23 mm²/s, P = 0.0004, and 1.97 × 10^?3 ± 0.43 mm²/s versus 1.48 × 10^?3 ± 0.29 mm²/s, P = 0.008, respectively). Colorectal wall thickness (r = 0.84, P < 0.0001), normalized T₂ signal intensity (r = 0.85, P < 0.0001) and ADC (r = 0.80, P < 0.0001) were strongly correlated with the histopathological inflammation score, whereas normalized T₁ signal intensity and D were moderately correlated (r = 0.64, P = 0.0006, and r = 0.65, P = 0.0003, respectively). High‐field MRI features of single‐dose radiation‐induced rectocolitis in rats differ significantly from those of control rats. Quantitative MRI characteristics, especially wall thickness, normalized T₂ signal intensity, ADC and D, are potential markers of the histopathological inflammation score.     

Investigation of field and diffusion time dependence of the diffusion‐weighted signal at ultrahigh magnetic fields

Over the last decade, there has been a significant increase in the number of high‐magnetic‐field MRI magnets. However, the exact effect of a high magnetic field strength (B₀) on diffusion‐weighted MR signals is not yet fully understood. The goal of this study was to investigate the influence of different high magnetic field strengths (9.4 T and 14.1 T) and diffusion times (9, 11, 13, 15, 17 and 24 ms) on the diffusion‐weighted signal in rat brain white matter. At a short diffusion time (9 ms), fractional anisotropy values were found to be lower at 14.1 T than at 9.4 T, but this difference disappeared at longer diffusion times. A simple two‐pool model was used to explain these findings. The model describes the white matter as a first hindered compartment (often associated with the extra‐axonal space), characterized by a faster orthogonal diffusion and a lower fractional anisotropy, and a second restricted compartment (often associated with the intra‐axonal space), characterized by a slower orthogonal diffusion (i.e. orthogonal to the axon direction) and a higher fractional anisotropy. Apparent T₂ relaxation time measurements of the hindered and restricted pools were performed. The shortening of the pseudo‐T₂ value from the restricted compartment with B₀ is likely to be more pronounced than the apparent T₂ changes in the hindered compartment. This study suggests that the observed differences in diffusion tensor imaging parameters between the two magnetic field strengths at short diffusion time may be related to differences in the apparent T₂ values between the pools. Copyright © 2013 John Wiley & Sons, Ltd.     

Effects of diffusion on high‐resolution quantitative T2 MRI

Carr–Purcell–Meiboom–Gill‐based sequences are often assumed to be insensitive to diffusion. However, imaging gradients always contribute some degree of diffusion weighting which increases with resolution. This may cause an apparent decrease in T₂ when using a multi‐echo sequence, such as quantitative T₂ (qT2) at high resolution. This study investigated the impact of diffusion on the qT2 sequence. An equation was developed relating the diffusion factor associated with each echo (b_qT2) to the underestimation of T₂, which was strongly dependent on both the actual T₂ and the apparent diffusion coefficient of the tissue. The diffusion dependence of the measured T₂ was demonstrated in rat spinal cord. The measured T₂ was independent of the imaging plane in gray matter, where diffusion was isotropic, and orientation dependent in white matter, where diffusion was strongly anisotropic. The dependence of the measured T₂ on the actual T₂ value was also demonstrated in MnCl₂ phantoms. The relationship between the resolution and underestimation of T₂ was investigated both theoretically and experimentally for the original readout and a fully refocused readout. The fully refocused readout increased the resolution at which diffusion effects could be neglected whilst measuring T₂. To avoid the misidentification of cerebrospinal fluid when applying qT2 in the brain or spinal cord, a minimum in‐plane voxel dimension of 0.2 mm was suggested for the standard qT2 sequence and 0.1 mm for the refocused readout. Simulations of myelin water fraction measurement indicated that signal‐to‐noise ratio requirements were increased in the presence of diffusion. Finally, the use of decreasing spoiler gradients to attenuate stimulated echoes should be avoided, as it was found to distort the T₂ distribution when the slice thickness was less than 1 mm. Copyright © 2014 John Wiley & Sons, Ltd.     

Noninvasive quantitative magnetization transfer MRI reveals tubulointerstitial fibrosis in murine kidney

Excessive tissue scarring, or fibrosis, is a critical contributor to end stage renal disease, but current clinical tests are not sufficient for assessing renal fibrosis. Quantitative magnetization transfer (qMT) MRI provides indirect information about the macromolecular composition of tissues. We evaluated measurements of the pool size ratio (PSR, the ratio of immobilized macromolecular to free water protons) obtained by qMT as a biomarker of tubulointerstitial fibrosis in a well‐established murine model with progressive renal disease. MR images were acquired from 16‐week‐old fibrotic hHB‐EGF^Tg/Tg mice and normal wild‐type (WT) mice (N = 12) at 7 T. QMT parameters were derived using a two‐pool five‐parameter fitting model. A normal range of PSR values in the cortex and outer stripe of outer medulla (CR + OSOM) was determined by averaging across voxels within WT kidneys (mean ± 2SD). Regions in diseased mice whose PSR values exceeded the normal range above a threshold value (tPSR) were identified and measured. The spatial distribution of fibrosis was confirmed using picrosirius red stains. Compared with normal WT mice, scattered clusters of high PSR regions were observed in the OSOM of hHB‐EGF^Tg/Tg mouse kidneys. Moderate increases in mean PSR (mPSR) of CR + OSOM regions were observed across fibrotic kidneys. The abnormally high PSR regions (% area) detected by the tPSR were significantly increased in hHB‐EGF^Tg/Tg mice, and were highly correlated with regions of fibrosis detected by histological fibrosis indices measured from picrosirius red staining. Renal tubulointerstitial fibrosis in OSOM can thus be assessed by qMT MRI using an appropriate analysis of PSR. This technique may be used as an imaging biomarker for chronic kidney diseases.