A comparison of arterial spin labeling perfusion MRI and DCE‐MRI in human prostate cancer

Perfusion MRI has the potential to provide pathophysiological biomarkers for the evaluating, staging and therapy monitoring of prostate cancer. The objective of this study was to explore the feasibility of noninvasive arterial spin labeling (ASL) to detect prostate cancer in the peripheral zone and to investigate the correlation between the blood flow (BF) measured by ASL and the pharmacokinetic parameters K^trans (forward volume transfer constant), k_ep (reverse reflux rate constant between extracellular space and plasma) and v_e (the fractional volume of extracellular space per unit volume of tissue) measured by dynamic contrast‐enhanced (DCE) MRI in patients with prostate cancer. Forty‐three consecutive patients (ages ranging from 49 to 86 years, with a median age of 74 years) with pathologically confirmed prostate cancer were recruited. An ASL scan with four different inversion times (TI = 1000, 1200, 1400 and 1600 ms) and a DCE‐MRI scan were performed on a clinical 3.0 T GE scanner. BF, K^trans, k_ep and v_e maps were calculated. In order to determine whether the BF values in the cancerous area were statistically different from those in the noncancerous area, an independent t‐test was performed. Spearman's bivariate correlation was used to assess the relationship between BF and the pharmacokinetic parameters K^trans, k_ep and v_e. The mean BF values in the cancerous areas (97.1 ± 30.7, 114.7 ± 28.7, 102.3 ± 22.5, 91.2 ± 24.2 ml/100 g/min, respectively, for TI = 1000, 1200, 1400, 1600 ms) were significantly higher (p < 0.01 for all cases) than those in the noncancerous regions (35.8 ± 12.5, 42.2 ± 13.7, 53.5 ± 19.1, 48.5 ± 13.5 ml/100 g/min, respectively). Significant positive correlations (p < 0.01 for all cases) between BF and the pharmacokinetic parameters K^trans, k_ep and v_e were also observed for all four TI values (r = 0.671, 0.407, 0.666 for TI = 1000 ms; 0.713, 0.424, 0.698 for TI = 1200 ms; 0.604, 0.402, 0.595 for TI = 1400 ms; 0.605, 0.422, 0.548 for TI = 1600 ms). It can be seen that the quantitative ASL measurements show significant differences between cancerous and benign tissues, and exhibit strong to moderate correlations with the parameters obtained using DCE‐MRI. These results show the promise of ASL as a noninvasive alternative to DCE‐MRI. Copyright © 2014 John Wiley & Sons, Ltd.     

Quantification of regional myocardial mean intracellular water lifetime: A nonhuman primate study in myocardial stress

Heart failure with preserved ejection fraction (HFpEF) is typically associated with early metabolic remodeling. Noninvasive imaging biomarkers that reflect these changes will be crucial in determining responses to early drug interventions in these patients. Mean intracellular water lifetime (τ_i) has been shown to be partially inversely related to Na, K‐ATPase transporter activity and may thus provide insight into the metabolic status in HFpEF patients. Here, we aim to perform regional quantification of τ_i using dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) in the nonhuman primate (NHP) heart and evaluate its region‐specific variations under conditions of myocardial stress in the context of perturbed myocardial function. Cardiac stress was induced in seven naïve cynomolgus macaques using a dobutamine stepwise infusion protocol. All animals underwent 3 T cardiac dual‐bolus DCE and tagging MRI experiments. The shutter‐speed model was employed to quantify regional τ_i from the DCE‐MR images. Additionally, τ_i values were correlated with myocardial strains. During cardiac stress, there was a significant decrease in global τ_i (192.9 ± 76.3 ms vs 321.6 ± 70 ms at rest, P < 0.05) in the left ventricle, together with an increase in global peak circumferential strain (?15.4% ± 2.7% vs ?10.1% ± 2.9% at rest, P < 0.05). Specifically, slice‐level analysis further revealed that a greater significant decrease in mean τ_i was observed in the apical region (Δτ_I = 182.4 ms) compared with the basal (Δτ_i = 113.2 ms) and midventricular regions (Δτ_i = 108.4 ms). Regional analysis revealed that there was a greater significant decrease in mean τ_i in the anterior (Δτ_i = 243.9 ms) and antero‐lateral (Δτ_i = 177.2 ms) regions. In the inferior and infero‐septal regions, although a decrease in τ_i was observed, it was not significant. Whole heart regional quantification of τ_i is feasible using DCE‐MRI. τ_i is sensitive to regional changes in metabolic state during cardiac stress, and its value correlates with strain.     

Correlative assessment of tumor microcirculation using contrast‐enhanced perfusion MRI and intravoxel incoherent motion diffusion‐weighted MRI: is there a link between them?

The purpose of this study was to correlate intravoxel incoherent motion (IVIM) imaging with classical perfusion‐weighted MRI metrics in human gliomas. Parametric images for slow diffusion coefficient (D), fast diffusion coefficient (D*), and fractional perfusion‐related volume (f) in patients with high‐grade gliomas were generated. Maps of F_p (plasma flow), v_p (vascular plasma volume), PS (permeability surface–area product), v_e (extravascular, extracellular volume), E (extraction ratio), k_e (influx ratio into the interstitium), and t_c (vascular transit time) from dynamic contrast‐enhanced (DCE) and dynamic susceptibility contrast‐enhanced (DSC) MRI were also generated. A region‐of‐interest analysis on the contralateral healthy white matter and on the tumor areas was performed and the extracted parameter values were tested for any significant differences among tumor grades or any correlations. Only f could be significantly correlated to DSC‐derived v_p and t_c in healthy brain tissue. Concerning the tumor regions, F_p was significantly positively correlated with D* and inversely correlated with f in DSC measurements. The D*, f, and f × D* values in the WHO grade III gliomas were non‐significantly different from those in the grade IV gliomas. There was a trend to significant negative correlations between f and PS as well as between f × D* and k_e in DCE experiments. Presumably due to different theoretical background, tracer properties and modeling of the tumor vasculature in the IVIM theory, there is no clearly evident link between D*, f and DSC‐ and DCE‐derived metrics. Copyright © 2014 John Wiley & Sons, Ltd.     

In vivo chlorine‐35, sodium‐23 and proton magnetic resonance imaging of the rat brain

In this study we demonstrate the feasibility of combined chlorine‐35, sodium‐23 and proton magnetic resonance imaging (MRI) at 9.4 Tesla, and present the first in vivo chlorine‐35 images obtained by means of MRI. With the experimental setup used in this study all measurements could be done in one session without changing the setup or moving the subject. The multinuclear measurement requires a total measurement time of 2 h and provides morphological (protons) and physiological (sodium‐23, chlorine‐35) information in one scanning session. Chlorine‐35, sodium‐23 and high resolution proton images were acquired from a phantom, a healthy rat and from a rat displaying a focal cerebral infarction. Compared to the healthy tissue a signal enhancement of a factor of 2.2 ± 0.2 in the chlorine‐35 and a factor of 2.9 ± 0.6 in the sodium‐23 images is observed in the areas of infarction. Exemplary unlocalized measurement of the in vivo longitudinal and transversal relaxation time of chlorine‐35 in a healthy rat showed multi‐exponential behaviour. A biexponential fit revealed a fast and a slow relaxing component with T_1,a = (1.7 ± 0.4) ms, T_1,b = (25.1 ± 1.4) ms, amplitudes of A = 0.26 ± 0.02, (1–A) = 0.74 ± 0.02 and T_2,a = (1.3 ± 0.1) ms, T_2,b = (11.8 ± 1.1) ms, A = 0.64 ± 0.02, (1–A) = 0.36 ± 0.02. Combined proton, sodium‐23 and chlorine‐35 MRI may provide a new approach for non‐invasive studies of ionic regulatory processes under physiological and pathological conditions in vivo. Copyright © 2010 John Wiley & Sons, Ltd.     

Simultaneous measurement of T1/B1 and pharmacokinetic model parameters using active contrast encoding (ACE)‐MRI

The aim of this study was to assess the feasibility of combining dynamic contrast enhanced‐magnetic resonance imaging (DCE‐MRI) with the measurement of the radiofrequency (RF) transmit field B ₁ and pre‐contrast longitudinal relaxation time T ₁₀. A novel approach has been proposed to simultaneously estimate B ₁ and T ₁₀ from a modified DCE‐MRI scan that actively encodes the washout phase of the curve with different amounts of T ₁ and B ₁ weighting using multiple flip angles and repetition times, hence referred to as active contrast encoding (ACE)‐MRI. ACE‐MRI aims to simultaneously measure B ₁ and T ₁₀, together with contrast kinetic parameters, such as the transfer constant K ^trans, interstitial space volume fraction v _e and vascular space volume fraction v _p. The proposed method was tested using numerical simulations and in vivo studies with mouse models of breast cancer implanted in the flank and mammary fat pad, and glioma in the brain. In the numerical simulation study with a signal‐to‐noise ratio of 10, both B ₁ and T ₁₀ were estimated accurately with errors of 5.1 ± 3.5% and 12.3 ± 8.8% and coefficients of variation (CV) of 14.9 ± 8.6% and 15.0 ± 5.0%, respectively. Using the same ACE‐MRI data, the kinetic parameters K ^trans, v _e and v _p were also estimated with errors of 14.2 ± 8.3% (CV = 13.5 ± 4.6%), 14.7 ± 9.9% (CV = 13.3 ± 4.5%) and 14.0 ± 9.3% (CV = 14.0 ± 4.5%), respectively. For the in vivo tumor data from 11 mice, voxel‐wise comparisons between ACE‐MRI and DCE‐MRI methods showed that the mean differences for the five parameters were as follows: ΔK ^trans = 0.006 (/min), Δv _e = 0.016, Δv _p = 0.000, ΔB ₁ = ?0.014 and ΔT ₁ = ?0.085 (s), which suggests a good agreement between the two methods. When compared with separately measured B ₁ and T ₁₀, and DCE‐MRI estimated kinetic parameters as a reference, the mean relative errors of ACE‐MRI estimation were B ₁ = ?0.3%, T ₁₀ = ?8.5%, K ^trans = 11.4%, v _e = 14.5% and v _p = 4.5%. This proof‐of‐concept study demonstrates that the proposed ACE‐MRI method can be used to estimate B ₁ and T ₁₀, together with contrast kinetic model parameters.     

Fast volumetric imaging of bound and pore water in cortical bone using three‐dimensional ultrashort‐TE (UTE) and inversion recovery UTE sequences

We report the three‐dimensional ultrashort‐TE (3D UTE) and adiabatic inversion recovery UTE (IR‐UTE) sequences employing a radial trajectory with conical view ordering for bi‐component T₂* analysis of bound water (T₂*^BW) and pore water (T₂*^PW) in cortical bone. An interleaved dual‐echo 3D UTE acquisition scheme was developed for fast bi‐component analysis of bound and pore water in cortical bone. A 3D IR‐UTE acquisition scheme employing multiple spokes per IR was developed for bound water imaging. Two‐dimensional UTE (2D UTE) and IR‐UTE sequences were employed for comparison. The sequences were applied to bovine bone samples (n = 6) and volunteers (n = 6) using a 3‐T scanner. Bi‐component fitting of 3D UTE images of bovine samples showed a mean T₂*^BW of 0.26 ± 0.04 ms and T₂*^PW of 4.16 ± 0.35 ms, with fractions of 21.5 ± 3.6% and 78.5 ± 3.6%, respectively. The 3D IR‐UTE signal showed a single‐component decay with a mean T₂*^BW of 0.29 ± 0.05 ms, suggesting selective imaging of bound water. Similar results were achieved with the 2D UTE and IR‐UTE sequences. Bi‐component fitting of 3D UTE images of the tibial midshafts of healthy volunteers showed a mean T₂*^BW of 0.32 ± 0.08 ms and T₂*^PW of 5.78 ± 1.24 ms, with fractions of 34.2 ± 7.4% and 65.8 ± 7.4%, respectively. Single‐component fitting of 3D IR‐UTE images showed a mean T₂*^BW of 0.35 ± 0.09 ms. The 3D UTE and 3D IR‐UTE techniques allow fast volumetric mapping of bound and pore water in cortical bone. Copyright © 2016 John Wiley & Sons, Ltd.     

Three‐dimensional ultrashort echo time cones T1ρ (3D UTE‐cones‐T1ρ) imaging

We report a novel three‐dimensional (3D) ultrashort echo time (UTE) sequence employing Cones trajectory and T_1ρ preparation (UTE‐Cones‐T_1ρ) for quantitative T_1ρ assessment of short T₂ tissues in the musculoskeletal system. A basic 3D UTE‐Cones sequence was combined with a spin‐locking preparation pulse for T_1ρ contrast. A relatively short TR was used to decrease the scan time, which required T₁ measurement and compensation using 3D UTE‐Cones data acquisitions with variable TRs. Another strategy to reduce the total scan time was to acquire multiple Cones spokes (N_sp) after each T_1ρ preparation and fat saturation. Four spin‐locking times (TSL = 0–20 ms) were acquired over 12 min, plus another 7 min for T₁ measurement. The 3D UTE‐Cones‐T_1ρ sequence was compared with a two‐dimensional (2D) spiral‐T_1ρ sequence for the imaging of a spherical CuSO₄ phantom and ex vivo meniscus and tendon specimens, as well as the knee and ankle joints of healthy volunteers, using a clinical 3‐T scanner. The CuSO₄ phantom showed a T_1ρ value of 76.5 ± 1.6 ms with the 2D spiral‐T_1ρ sequence, as well as 85.7 ± 3.6 and 89.2 ± 1.4 ms for the 3D UTE‐Cones‐T_1ρ sequences with N_sp of 1 and 5, respectively. The 3D UTE‐Cones‐T_1ρ sequence provided shorter T_1ρ values for the bovine meniscus sample relative to the 2D spiral‐T_1ρ sequence (10–12 ms versus 16 ms, respectively). The cadaveric human Achilles tendon sample could only be imaged with the 3D UTE‐Cones‐T_1ρ sequence (T_1ρ = 4.0 ± 0.9 ms), with the 2D spiral‐T_1ρ sequence demonstrating near‐zero signal intensity. Human studies yielded T_1ρ values of 36.1 ± 2.9, 18.3 ± 3.9 and 3.1 ± 0.4 ms for articular cartilage, meniscus and the Achilles tendon, respectively. The 3D UTE‐Cones‐T_1ρ sequence allows volumetric T_1ρ measurement of short T₂ tissues in vivo.     

MRI quantification of non‐Gaussian water diffusion in normal human kidney: a diffusional kurtosis imaging study

Our aim was to prospectively evaluate the feasibility of diffusional kurtosis imaging (DKI) in normal human kidney and to report preliminary DKI measurements. Institutional review board approval and informed consent were obtained. Forty‐two healthy volunteers underwent diffusion‐weighted imaging (DWI) scans with a 3‐T MR scanner. b values of 0, 500 and 1000 s/mm² were adopted. Maps of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (D_⊥), axial diffusivity (D_||), mean kurtosis (MK), radial kurtosis (K_⊥) and axial kurtosis (K_||) were produced. Three representative axial slices in the upper pole, mid‐zone and lower pole were selected in the left and right kidney. On each selected slice, three regions of interest were drawn on the renal cortex and another three on the medulla. Statistical comparison was performed with t‐test and analysis of variance. Thirty‐seven volunteers successfully completed the scans. No statistically significant differences were observed between the left and right kidney for all metrics (p values in the cortex: FA, 0.114; MD, 0.531; D_⊥, 0.576; D_||, 0.691; MK, 0.934; K_⊥, 0.722; K_||, 0.891; p values in the medulla: FA, 0.348; MD, 0.732; D_⊥, 0.470; D_||, 0.289; MK, 0.959; K_⊥, 0.780; K_||, 0.287). Kurtosis metrics (MK, K_||, K_⊥) obtained in the renal medulla were significantly (p <0.001) higher than those in the cortex (0.552 ± 0.04, 0.637 ± 0.07 and 0.530 ± 0.08 in the medulla and 0.373 ± 0.04, 0.492 ± 0.06 and 0.295 ± 0.06 in the cortex, respectively). For the diffusivity measures, FA of the medulla (0.356 ± 0.03) was higher than that of the cortex (0.179 ± 0.03), whereas MD, D_⊥ and D_|| (mm²/ms) were lower in the medulla than in the cortex (3.88 ± 0.09, 3.50 ± 0.23 and 4.65 ± 0.29 in the cortex and 2.88 ± 0.11, 2.32 ± 0.20 and 3.47 ± 0.31 in the medulla, respectively). Our results indicate that DKI is feasible in the human kidney. We have reported the preliminary DKI measurements of normal human kidney that demonstrate well the non‐Gaussian behavior of water diffusion, especially in the renal medulla. Copyright © 2014 John Wiley & Sons, Ltd.     

Bi‐exponential 23Na T2* component analysis in the human brain

The purpose of this study was to measure the sodium transverse relaxation time T₂* in the healthy human brain. Five healthy subjects were scanned with 18 echo times (TEs) as short as 0.17 ms. T₂* values were fitted on a voxel‐by‐voxel basis using a bi‐exponential model. Data were also analysed using a continuous distribution fit with a region of interest‐based inverse Laplace transform. Average T₂* values were 3.4 ± 0.2 ms and 23.5 ± 1.8 ms in white matter (WM) for the short and long components, respectively, and 3.9 ± 0.5 ms and 26.3 ± 2.6 ms in grey matter (GM) for the short and long components, respectively, using the bi‐exponential model. Continuous distribution fits yielded results of 3.1 ± 0.3 ms and 18.8 ± 3.2 ms in WM for the short and long components, respectively, and 2.9 ± 0.4 ms and 17.2 ± 2 ms in GM for the short and long components, respectively. ²³Na T₂* values of the brain for the short and long components for various anatomical locations using ultra‐short TEs are presented for the first time.     

Gaussian mixture model‐based classification of dynamic contrast enhanced MRI data for identifying diverse tumor microenvironments: preliminary results

Tumor hypoxia develops heterogeneously, affects radiation sensitivity and the development of metastases. Prognostic information derived from the in vivo characterization of the spatial distribution of hypoxic areas in solid tumors can be of value for radiation therapy planning and for monitoring the early treatment response. Tumor hypoxia is caused by an imbalance between the supply and consumption of oxygen. The tumor oxygen supply is inherently linked to its vasculature and perfusion which can be evaluated by dynamic contrast enhanced (DCE‐) MRI using the contrast agent Gd‐DTPA. Thus, we hypothesize that DCE‐MRI data may provide surrogate information regarding tumor hypoxia. In this study, DCE‐MRI data from a rat prostate tumor model were analysed with a Gaussian mixture model (GMM)‐based classification to identify perfused, hypoxic and necrotic areas for a total of ten tumor slices from six rats, of which one slice was used as training data for GMM classifications. The results of pattern recognition analyzes were validated by comparison to corresponding Ak_ep maps defining the perfused area (0.84 ± 0.09 overlap), hematoxylin and eosin (H&E)‐stained tissue sections defining necrosis (0.64 ± 0.15 overlap) and pimonidazole‐stained sections defining hypoxia (0.72 ± 0.17 overlap), respectively. Our preliminary data indicate the feasibility of a GMM‐based classification to identify tumor hypoxia, necrosis and perfusion/permeability from non‐invasively acquired, in vivo DCE‐MRI data alone, possibly obviating the need for invasive procedures, such as biopsies, or exposure to radioactivity, such as positron emission tomography (PET) exams. Copyright © 2013 John Wiley & Sons, Ltd.     

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.     

Predictive accuracy of single‐ and multi‐slice MRI for the estimation of total visceral adipose tissue in overweight to severely obese patients

The quantification of visceral adipose tissue (VAT) is increasingly being considered for risk assessment and treatment monitoring in obese patients, but is generally time‐consuming. The goals of this work were to semi‐automatically segment and quantify VAT areas of MRI slices at previously proposed anatomical landmarks and to evaluate their predictive power for whole‐abdominal VAT volumes on a relatively large number of patients. One‐hundred and ninety‐seven overweight to severely obese patients (65 males; body mass index, 33.3 ± 3.5 kg/m²; 132 females; body mass index, 34.3 ± 3.2 kg/m²) underwent MRI examination. Total VAT volumes (V_VAT‐T) of the abdominopelvic cavity were quantified by retrospective analysis of two‐point Dixon MRI data (active‐contour segmentation, visual correction and histogram analysis). V_VAT‐T was then compared with VAT areas determined on one or five slices defined at seven anatomical landmarks (lumbar intervertebral spaces, umbilicus and femoral heads) and corresponding conversion factors were determined. Statistical measures were the coefficients of variation and standard deviations σ₁ and σ₅ of the difference between predicted and measured VAT volumes (Bland–Altman analysis). V_VAT‐T was 6.0 ± 2.0 L (2.5–11.2 L) for males and 3.2 ± 1.4 L (0.9–7.7 L) for females. The analysis of five slices yielded a better agreement than the analysis of single slices, required only a little extra time (4 min versus 2 min) and was substantially faster than whole‐abdominal assessment (24 min). Best agreements were found at intervertebral spaces L3–L4 for females (σ_5/1 = 523/608 mL) and L2–L3 for males (σ_5/1 = 613/706 mL). Five‐slice VAT volume estimates at the level of lumbar disc L3–L4 for females and L2–L3 for males can be obtained within 4 min and were a reliable predictor for abdominopelvic VAT volume in overweight to severely adipose patients. One‐slice estimates took only 2 min and were slightly less accurate. These findings may contribute to the implementation of analytical methods for fast and reliable (routine) estimation of VAT volumes in obese patients. Copyright © 2015 John Wiley & Sons, Ltd.     

Evaluation of short‐TE 1H MRSI for quantification of metabolites in the prostate

Back‐to‐back ¹H MRSI scans, using an endorectal and phased‐array coil combination, were performed on 18 low‐risk patients with prostate cancer at 3 T, employing TEs of 32 and 100 ms in order to compare metabolite visualization at each TE. Outer‐volume suppression of lipid signals was performed using regional saturation (REST) slabs and the quantification of spectra at both TEs was achieved with the quantitation using quantum estimation (QUEST) routine. Metabolite nulling experiments in an additional five patients found that there were negligible macromolecule background signals in prostate spectra at TE = 32 ms. Metabolite visibility was judged using the criterion Cramér–Rao lower bound (CRLB)/amplitude < 20%, and metabolite concentrations were corrected for relaxation effects and referenced to the data acquired in corresponding water‐unsuppressed MRSI scans. For the first time, the prostate metabolites spermine and myo‐inositol were quantified individually in vivo, together with citrate, choline and creatine. All five metabolite visibilities were higher in TE = 32 ms MRSI than in TE = 100 ms MRSI. At TE = 32 ms, citrate was visible in 99.0% of lipid‐free spectra, whereas, at TE = 100 ms, no metabolite simulation of citrate matched the in vivo peaks. Spermine, choline and creatine were visualised separately in 30.4% more spectra at TE = 32 ms than at TE = 100 ms, and myo‐inositol in 72.5% more spectra. T₂ values were calculated for spermine (53 ± 16 ms), choline (62 ± 17 ms) and myo‐inositol (90 ± 48 ms). Data from the TE = 32 ms spectra showed that the concentrations of citrate and spermine secretions were positively correlated in both the peripheral zone and central gland (R² = 0.73 and R² = 0.43, respectively), and that the citrate content was significantly higher in the former at 64 ± 22 mm than in the latter at 32 ± 16 mm (p = 0.01). However, lipid contamination at TE = 32 ms was substantial; therefore, to make clinical use of the greater visualisation of prostate metabolites at TE = 32 ms rather than at TE = 100 ms, three‐dimensional MRSI at TE = 32 ms with effective lipid suppression must be implemented. ©2014 The Authors. NMR in Biomedicine published by 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.     

Adenosine induces prolonged anti‐β‐adrenergic effects in guinea‐pig papillary muscle

A sustained anti‐β‐adrenergic effect of adenosine has been reported. This study was initiated to investigate this topic and especially elucidate the role of protein kinase C (PKC). Contractile force amplitude and action potential duration at 90% repolarization (APD₉₀) were measured in guinea‐pig papillary muscles before and after 5 min challenge with 5 nm isoproterenol. Protocols contained 30 min exposure to the test agents adenosine 33 μm (ado), adenosine + PKC‐inhibitor bisindolylmaleimide 20 nM (ado + BIM), PKC‐activator 1,2‐dioctanoyl‐sn‐glycerol 10 μm (DOG) and α‐agonist phenylephrine 5 μm (phe). Isoproterenol was given at the end of test exposure and after 15 min washout. Results are mean ± SEM of percentage‐change, P ≤ 0.05 considered significant and labelled *. The first isoproterenol challenge significantly increased contractile force (27 ± 7%*) in the control group. Responses in the test groups were 2 ± 4 (ado), 1 ± 5 (ado + BIM), 14 ± 4* (DOG), 0 ± 2% (phe). After washout of adenosine, DOG and phenylephrine, isoproterenol induced 3 ± 8 (ado), 23 ± 5* (ado + BIM), 13 ± 5* (DOG), 15 ± 7% (phe) increase in test groups compared with 22 ± 5%* increase in contractile force in the control group. After 45 min washout of adenosine the inotropic response was still significantly reduced compared with control (29 ± 4 vs. 79 ± 8%*). Isoproterenol stimulation shortened APD₉₀ in controls at both time points (5 ± 1%* and 4 ± 1%*), with no significant shortening in test groups. Adenosine induces sustained anti‐β‐adrenergic effects on contractile force as well as APD₉₀. A role for PKC in signal transduction is supported with respect to contractile force.     

In vivo detection of the effects of preconditioning on LNCaP tumors by a TNF‐α nanoparticle construct using MRI

The outcome of systemic and local therapies (e.g. chemotherapy, radiotherapy, surgery, focal ablation) for prostate cancer can be significantly improved by using tumor‐specific adjuvants prior to treatment (“preconditioning”). We propose to use dynamic contrast enhanced magnetic resonance imaging (DCE‐MRI) to monitor the in vivo response of a mouse model of prostate cancer treated with a vascular disruptive agent, TNF‐α, delivered on a gold nanoparticle (NP‐TNF). Six male nude mice bearing 4–5 week old LNCaP tumors were scanned at 9.4 T. DCE‐MRI was performed two days before and 4–5 h after treatment with NP‐TNF. An intraperitoneal (i.p.) bolus of gadolinium‐DTPA (Gd) was administered and contrast enhancement was measured for 90 min. Concentration–time curves of Gd were calculated and the area under the Gd curve (AUGC) was determined pre‐ and post‐treatment. NP‐TNF treatment caused an increase in contrast uptake in tumors. Interestingly, the early concentration (10 min post Gd bolus i.p.) was similar in both untreated and treated conditions; however, 90 min after injection, [Gd] was 3.4 times higher than before treatment. AUGC doubled from (11 ± 6) [Gd] × min before treatment to (22 ± 9) [Gd] × min after treatment. An increase in signal enhancement was also observed in the muscle but to a lesser degree. We also evaluated the kinetics of intravenous Gd administration in mice bearing a jugular vein catheter to mimic the delivery method used in clinical trials. The overall treatment effects were independent of the delivery pathway of the contrast agent. In conclusion, we show that DCE‐MRI is suitable to detect changes associated with a vascular disruptive agent in a mouse model of prostate cancer. The ability to characterize the effects of nanoparticle therapy in vivo with non‐destructive methods is important, as such compounds, in combination with treatment strategies, are progressing towards clinical trials. Copyright © 2014 John Wiley & Sons, Ltd.     

Adiabatic multi‐echo 31P spectroscopic imaging (AMESING) at 7 T for the measurement of transverse relaxation times and regaining of sensitivity in tissues with short T2* values

An adiabatic multi‐echo spectroscopic imaging (AMESING) sequence, used for ³¹P MRSI, with spherical k‐space sampling and compensated phase‐encoding gradients, was implemented on a whole‐body 7‐T MR system. One free induction decay (FID) and up to five symmetric echoes can be acquired with this sequence. In tissues with low T₂* and high T₂, this can theoretically lead to a potential maximum signal‐to‐noise ratio (SNR) increase of almost a factor of three, compared with a conventional FID acquisition with Ernst‐angle excitation. However, with T₂ values being, in practice, ≤400 ms, a maximum enhancement of approximately two compared with low flip Ernst‐angle excitation should be feasible. The multi‐echo sequence enables the determination of localized T₂ values, and was validated with ³¹P three‐dimensional MRSI on the calf muscle and breast of a healthy volunteer, and subsequently applied in a patient with breast cancer. The T₂ values of phosphocreatine, phosphodiesters (PDE) and inorganic phosphate in calf muscle were 193 ± 5 ms, 375 ± 44 ms and 96 ± 10 ms, respectively, and the apparent T₂ value of γ‐ATP was 25 ± 6 ms. A T₂ value of 136 ± 15 ms for inorganic phosphate was measured in glandular breast tissue of a healthy volunteer. The T₂ values of phosphomonoesters (PME) and PDE in breast cancer tissue (ductulolobular carcinoma) ranged between 170 and 210 ms, and the PME to PDE ratios were calculated to be phosphoethanolamine/glycerophosphoethanolamine = 2.7, phosphocholine/glycerophosphocholine = 1.8 and PME/PDE = 2.3. Considering the relatively short T₂* values of the metabolites in breast tissue at 7 T, the echo spacing can be short without compromising spectral resolution, whilst maximizing the sensitivity. Copyright © 2013 John Wiley & Sons, Ltd.     

Evaluation of bound and pore water in cortical bone using ultrashort‐TE MRI

Bone water exists in different states with the majority bound to the organic matrix and to mineral, and a smaller fraction in ‘free’ form in the pores of cortical bone. In this study, we aimed to develop and evaluate ultrashort‐TE (UTE) MRI techniques for the assessment of T₂*, T₁ and concentration of collagen‐bound and pore water in cortical bone using a 3‐T clinical whole‐body scanner. UTE MRI, together with an isotope study using tritiated and distilled water (THO–H₂O) exchange, as well as gravimetric analysis, were performed on ten sectioned bovine bone samples. In addition, 32 human cortical bone samples were prepared for comparison between the pore water concentration measured with UTE MRI and the cortical porosity derived from micro‐computed tomography (μCT). A short T₂* of 0.27 ± 0.03 ms and T₁ of 116 ± 6 ms were observed for collagen‐bound water in bovine bone. A longer T₂* of 1.84 ± 0.52 ms and T₁ of 527 ± 28 ms were observed for pore water in bovine bone. UTE MRI measurements showed a pore water concentration of 4.7–5.3% by volume and collagen‐bound water concentration of 15.7–17.9% in bovine bone. THO–H₂O exchange studies showed a pore water concentration of 5.9 ± 0.6% and collagen‐bound water concentration of 18.1 ± 2.1% in bovine bone. Gravimetric analysis showed a pore water concentration of 6.3 ± 0.8% and collagen‐bound water concentration of 19.2 ± 3.6% in bovine bone. A mineral water concentration of 9.5 ± 0.6% was derived in bovine bone with the THO–H₂O exchange study. UTE‐measured pore water concentration is highly correlated (R² = 0.72, p < 0.0001) with μCT porosity in the human cortical bone study. Both bovine and human bone studies suggest that UTE sequences could reliably measure collagen‐bound and pore water concentration in cortical bone using a clinical scanner. Copyright © 2015 John Wiley & Sons, Ltd.     

Feasibility of quantitative ultrashort echo time (UTE)‐based methods for MRI of peripheral nerve

Peripheral nerves are a composite tissue consisting of neurovascular elements packaged within a well‐organized extracellular matrix. Their composition, size, and anatomy render nerves a challenging medical imaging target. In contrast to morphological MRI, which represents the predominant approach to nerve imaging, quantitative MRI sequences can provide information regarding tissue composition. Here, we applied standard clinical Carr‐Purcell‐Meiboom‐Gill (CPMG) and experimental three‐dimensional (3D) ultrashort echo time (UTE) Cones sequences for quantitative nerve imaging including T₂ measurement with single‐component analysis, T₂* measurement with single‐component and bi‐component analyses, and magnetization transfer ratio (MTR) analysis. We demonstrated the feasibility and the high quality of single‐component T₂*, bi‐component T₂*, and MTR approaches to analyze nerves imaged with clinically deployed 3D UTE Cones pulse sequences. For 24 single fascicles from eight nerves, we measured a mean single‐component T₂* of 22.6 ±8.9 ms, and a short T₂* component (STC) with a mean T₂* of 1.7 ±1.0 ms and a mean fraction of (6.74 ±4.31)% in bi‐component analysis. For eight whole nerves, we measured a mean single‐component T₂* of 16.7 ±2.2 ms, and an STC with a mean T₂* of 3.0 ±1.0 ms and a mean fraction of (15.56 ±7.07)% in bi‐component analysis. For nine fascicles from three healthy nerves, we measured a mean MTR of (25.2 ±1.9)% for single fascicles and a mean MTR of (23.6 ±0.9)% for whole nerves. No statistically significant correlation was observed between any MRI parameter and routine histological outcomes, perhaps due to the small sample size and lack of apparent sample pathology. Overall, we have successfully demonstrated the feasibility of measuring quantitative MR outcomes ex vivo, which might reflect features of nerve structure and macromolecular content. These methods should be validated comprehensively on a larger and more diverse set of nerve samples, towards the interpretation of in vivo outcomes. These approaches have new and broad implications for the management of nerve disease, injury, and repair.     

Additive hypothermic effects of the 5‐HT1A receptor agonist 8‐OH‐DPAT and the dopamine D2/3 receptor agonist 7‐OH‐DPAT in the rat

The objective of this study was to examine possible interactions between serotonergic and dopaminergic agents lowering core temperature via stimulation of 5‐HT_1A and dopamine (DA) D₂ receptors, respectively. The effects of the 5‐HT_1A receptor agonist (±)‐8‐hydroxy‐2‐(di‐n‐propylamino)tetralin HBr (8‐OH‐DPAT) and the DA D_2/3 receptor agonist 7‐OH‐DPAT on core temperature was monitored in adult male Wistar rats, approximately 300 g body weight. The temperature probe was connected to a PC‐assisted temperature instrument, and an automated printer device was activated when the temperature reading had stabilized (±0.1 °C) for 10 s. As expected, 7‐OH‐DPAT [0.5 and 2.0 μmol kg^–1 subcutaneous (s.c.)] as well as 8‐OH‐DPAT (0.15–2.4 μmol kg^–1 s.c.), produced a dose‐dependent hypothermia. When combined, there were additive effects of the two compounds, although the effects of 7‐OH‐DPAT were attenuated by 8‐OH‐DPAT at the higher doses (0.6–2.4 μmol kg^–1), in all probability because of emerging DA D₂ receptor blocking properties of the latter compound.