The impact of water exchange on estimates of myocardial extracellular volume calculated using contrast enhanced T1 measurements: A preliminary analysis in patients with severe aortic stenosis.

PURPOSE: Guidelines recommend measuring myocardial extracellular volume (ECV) using T1 -mapping before and 10-30 min after contrast agent administration. Data are then analyzed using a linear model (LM), which assumes fast water exchange (WX) between the ECV and cardiomyocytes. We investigated whether limited WX influences ECV measurements in patients with severe aortic stenosis (AS). METHODS: Twenty-five patients with severe AS and 5 healthy controls were recruited. T1 measurements were made on a 3 T Siemens system using a multiparametric saturation-recovery single-shot acquisition (a) before contrast; (b) 4 min post 0.05 mmol/kg gadobutrol; and (c) 4 min, (d) 10 min, and (e) 30 min after an additional gadobutrol dose (0.1 mmol/kg). Three LM-based ECV estimates, made using paired T1 measurements (a and b), (a and d), and (a and e), were compared to ECV estimates made using all 5 T1 measurements and a two-site exchange model (2SXM) accounting for WX. RESULTS: Median (range) ECV estimated using the 2SXM model was 25% (21%-39%) for patients and 26% (22%-29%) for controls. ECV estimated in patients using the LM at 10 min following a cumulative contrast dose of 0.15 mmol/kg was 21% (17%-32%) and increased significantly to 22% (19%-35%) at 30 min (p = 0.0001). ECV estimated using the LM was highest following low dose gadobutrol, 25% (19%-38%). CONCLUSION: Current guidelines on contrast agent dose for ECV measurements may lead to underestimated ECV in patients with severe AS because of limited WX. Use of a lower contrast agent dose may mitigate this effect.

A community-endorsed open-source lexicon for contrast agent-based perfusion MRI: A consensus guidelines report from the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).

This manuscript describes the ISMRM OSIPI (Open Science Initiative for Perfusion Imaging) lexicon for dynamic contrast-enhanced and dynamic susceptibility-contrast MRI. The lexicon was developed by Taskforce 4.2 of OSIPI to provide standardized definitions of commonly used quantities, models, and analysis processes with the aim of reducing reporting variability. The taskforce was established in February 2020 and consists of medical physicists, engineers, clinicians, data and computer scientists, and DICOM (Digital Imaging and Communications in Medicine) standard experts. Members of the taskforce collaborated via a slack channel and quarterly virtual meetings. Members participated by defining lexicon items and reporting formats that were reviewed by at least two other members of the taskforce. Version 1.0.0 of the lexicon was subject to open review from the wider perfusion imaging community between January and March 2022, and endorsed by the Perfusion Study Group of the ISMRM in the summer of 2022. The initial scope of the lexicon was set by the taskforce and defined such that it contained a basic set of quantities, processes, and models to enable users to report an end-to-end analysis pipeline including kinetic model fitting. We also provide guidance on how to easily incorporate lexicon items and definitions into free-text descriptions (e.g., in manuscripts and other documentation) and introduce an XML-based pipeline encoding format to encode analyses using lexicon definitions in standardized and extensible machine-readable code. The lexicon is designed to be open-source and extendable, enabling ongoing expansion of its content. We hope that widespread adoption of lexicon terminology and reporting formats described herein will increase reproducibility within the field.

Physiological confounders of renal blood flow measurement.

OBJECTIVES: Renal blood flow (RBF) is controlled by a number of physiological factors that can contribute to the variability of its measurement. The purpose of this review is to assess the changes in RBF in response to a wide range of physiological confounders and derive practical recommendations on patient preparation and interpretation of RBF measurements with MRI. METHODS: A comprehensive search was conducted to include articles reporting on physiological variations of renal perfusion, blood and/or plasma flow in healthy humans. RESULTS: A total of 24 potential confounders were identified from the literature search and categorized into non-modifiable and modifiable factors. The non-modifiable factors include variables related to the demographics of a population (e.g. age, sex, and race) which cannot be manipulated but should be considered when interpreting RBF values between subjects. The modifiable factors include different activities (e.g. food/fluid intake, exercise training and medication use) that can be standardized in the study design. For each of the modifiable factors, evidence-based recommendations are provided to control for them in an RBF-measurement. CONCLUSION: Future studies aiming to measure RBF are encouraged to follow a rigorous study design, that takes into account these recommendations for controlling the factors that can influence RBF results.

Evaluation of Monoexponential, Stretched-Exponential and Intravoxel Incoherent Motion MRI Diffusion Models in Early Response Monitoring to Neoadjuvant Chemotherapy in Patients With Breast Cancer-A Preliminary Study.

BACKGROUND: There has been a growing interest in exploring the applications of stretched-exponential (SEM) and intravoxel incoherent motion (IVIM) models of diffusion-weighted imaging (DWI) in breast imaging, with the focus on differentiation of breast lesions. However, the use of SEM and IVIM models to predict early response to neoadjuvant chemotherapy (NACT) has received less attention. PURPOSE: To investigate the value of monoexponential, SEM, and IVIM models to predict early response to NACT in patients with primary breast cancer. STUDY TYPE: Prospective. POPULATION: Thirty-seven patients with primary breast cancer (aged 46 ± 11 years) due to undergo NACT. FIELD STRENGTH/SEQUENCES: A 1.5-T MR scanner, T1 -weighted three-dimensional spoiled gradient-echo, two-dimensional single-shot spin-echo echo-planar imaging sequence (DWI) at six b-values (0-800 s mm-2 ). ASSESSMENT: Tumor volume, apparent diffusion coefficient, tissue diffusion (Dt ), pseudo-diffusion coefficient (Dp ), perfusion fraction (f), distributed diffusion coefficient, and alpha (α) were extracted, following volumetric sampling of the tumors, at three time-points: pretreatment, post one and three cycles of NACT. STATISTICAL TESTS: Mann-Whitney test, receiver operating characteristic (ROC) curve. Statistical significance level was P < 0.05. RESULTS: Following NACT, 17 patients were determined to be pathological responders and 20 nonresponders. Tumor volume was significantly larger in nonresponders at each MRI time-point and demonstrated reasonable performance in predicting response (area under the ROC curve [AUC] = 0.83-0.87). No significant differences between groups were found in the diffusion coefficients at each time-point (P = 0.09-1). The parameters α (SEM), f, and f × Dp (IVIM) were able to differentiate between response groups after one cycle of NACT (AUC = 0.73, 0.72, and 0.74, respectively). CONCLUSION: Diffusion coefficients derived from the monoexponential, SEM, and IVIM models did not predict pathological response. However, the IVIM-derived parameters f and f × Dp and the SEM-derived parameter α were able to predict response to NACT in breast cancer patients following one cycle of NACT. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Bias and Precision in Magnetic Resonance Imaging-Based Estimates of Renal Blood Flow: Assessment by Triangulation.

BACKGROUND: Renal blood flow (RBF) can be measured with dynamic contrast enhanced-MRI (DCE-MRI) and arterial spin labeling (ASL). Unfortunately, individual estimates from both methods vary and reference-standard methods are not available. A potential solution is to include a third, arbitrating MRI method in the comparison. PURPOSE: To compare RBF estimates between ASL, DCE, and phase contrast (PC)-MRI. STUDY TYPE: Prospective. POPULATION: Twenty-five patients with type-2 diabetes (36% female) and five healthy volunteers (HV, 80% female). FIELD STRENGTH/SEQUENCES: A 3 T; gradient-echo 2D-DCE, pseudo-continuous ASL (pCASL) and cine 2D-PC. ASSESSMENT: ASL, DCE, and PC were acquired once in all patients. ASL and PC were acquired four times in each HV. RBF was estimated and split-RBF was derived as (right kidney RBF)/total RBF. Repeatability error (RE) was calculated for each HV, RE = 1.96 × SD, where SD is the standard deviation of repeat scans. STATISTICAL TESTS: Paired t-tests and one-way analysis of variance (ANOVA) were used for statistical analysis. The 95% confidence interval (CI) for difference between ASL/PC and DCE/PC was assessed using two-sample F-test for variances. Statistical significance level was P < 0.05. Influential outliers were assessed with Cook's distance (Di > 1) and results with outliers removed were presented. RESULTS: In patients, the mean RBF (mL/min/1.73m2 ) was 618 ± 62 (PC), 526 ± 91 (ASL), and 569 ± 110 (DCE). Differences between measurements were not significant (P = 0.28). Intrasubject agreement was poor for RBF with limits-of-agreement (mL/min/1.73m2 ) [-687, 772] DCE-ASL, [-482, 580] PC-DCE, and [-277, 460] PC-ASL. The difference PC-ASL was significantly smaller than PC-DCE, but this was driven by a single-DCE outlier (P = 0.31, after removing outlier). The difference in split-RBF was comparatively small. In HVs, mean RE (±95% CI; mL/min/1.73 m2 ) was significantly smaller for PC (79 ± 41) than for ASL (241 ± 85). CONCLUSIONS: ASL, DCE, and PC RBF show poor agreement in individual subjects but agree well on average. Triangulation with PC suggests that the accuracy of ASL and DCE is comparable. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Motion correction of free-breathing magnetic resonance renography using model-driven registration.

INTRODUCTION: Model-driven registration (MDR) is a general approach to remove patient motion in quantitative imaging. In this study, we investigate whether MDR can effectively correct the motion in free-breathing MR renography (MRR). MATERIALS AND METHODS: MDR was generalised to linear tracer-kinetic models and implemented using 2D or 3D free-form deformations (FFD) with multi-resolution and gradient descent optimization. MDR was evaluated using a kidney-mimicking digital reference object (DRO) and free-breathing patient data acquired at high temporal resolution in multi-slice 2D (5 patients) and 3D acquisitions (8 patients). Registration accuracy was assessed using comparison to ground truth DRO, calculating the Hausdorff distance (HD) between ground truth masks with segmentations and visual evaluation of dynamic images, signal-time courses and parametric maps (all data). RESULTS: DRO data showed that the bias and precision of parameter maps after MDR are indistinguishable from motion-free data. MDR led to reduction in HD (HDunregistered = 9.98 ± 9.76, HDregistered = 1.63 ± 0.49). Visual inspection showed that MDR effectively removed motion effects in the dynamic data, leading to a clear improvement in anatomical delineation on parametric maps and a reduction in motion-induced oscillations on signal-time courses. DISCUSSION: MDR provides effective motion correction of MRR in synthetic and patient data. Future work is needed to compare the performance against other more established methods.

The benefit of MR-only radiotherapy treatment planning for anal and rectal cancers: A planning study.

INTRODUCTION: Limited evidence exists showing the benefit of magnetic resonance (MR)-only radiotherapy treatment planning for anal and rectal cancers. This study aims to assess the impact of MR-only planning on target volumes (TVs) and treatment plan doses to organs at risks (OARs) for anal and rectal cancers versus a computed tomography (CT)-only pathway. MATERIALS AND METHODS: Forty-six patients (29 rectum and 17 anus) undergoing preoperative or radical external beam radiotherapy received CT and T2 MR simulation. TV and OARs were delineated on CT and MR, and volumetric arc therapy treatment plans were optimized independently (53.2 Gy/28 fractions for anus, 45 Gy/25 fractions for rectum). Further treatment plans assessed gross tumor volume (GTV) dose escalation. Differences in TV volumes and OAR doses, in terms of Vx Gy (organ volume (%) receiving x dose (Gy)), were assessed. RESULTS: MR GTV and primary planning TV (PTV) volumes systematically reduced by 13 cc and 98 cc (anus) and 44 cc and 109 cc (rectum) respectively compared to CT volumes. Statistically significant OAR dose reductions versus CT were found for bladder and uterus (rectum) and bladder, penile bulb, and genitalia (anus). With GTV boosting, statistically significant dose reductions were found for sigmoid, small bowel, vagina, and penile bulb (rectum) and vagina (anus). CONCLUSION: Our findings provide evidence that the introduction of MR (whether through MR-only or CT-MR pathways) to radiotherapy treatment planning for anal and rectal cancers has the potential to improve treatments. MR-related OAR dose reductions may translate into less treatment-related toxicity for patients or greater ability to dose escalate.

Consensus-based technical recommendations for clinical translation of renal T1 and T2 mapping MRI.

To develop technical recommendations on the acquisition and post-processing of renal longitudinal (T1) and transverse (T2) relaxation time mapping. A multidisciplinary panel consisting of 18 experts in the field of renal T1 and T2 mapping participated in a consensus project, which was initiated by the European Cooperation in Science and Technology Action PARENCHIMA CA16103. Consensus recommendations were formulated using a two-step modified Delphi method. The first survey consisted of 56 items on T1 mapping, of which 4 reached the pre-defined consensus threshold of 75% or higher. The second survey was expanded to include both T1 and T2 mapping, and consisted of 54 items of which 32 reached consensus. Recommendations based were formulated on hardware, patient preparation, acquisition, analysis and reporting. Consensus-based technical recommendations for renal T1 and T2 mapping were formulated. However, there was considerable lack of consensus for renal T1 and particularly renal T2 mapping, to some extent surprising considering the long history of relaxometry in MRI, highlighting key knowledge gaps that require further work. This paper should be regarded as a first step in a long-term evidence-based iterative process towards ever increasing harmonization of scan protocols across sites, to ultimately facilitate clinical implementation.

Shutter-speed dynamic contrast-enhanced MRI: Is it fit for purpose?

PURPOSE: To test the ability of shutter-speed dynamic contrast-enhanced (DCE) MRI to estimate water exchange (WX) using simulations and assess its performance in clinical case studies of malignant and benign breast tumors. METHODS: Data were simulated using a 1-compartment tracer kinetic (TK) model combined with a 2-pool WX model (2PX) and with a 2-compartment TK model. Typical DCE-MRI acquisition parameters were used with both WX-sensitive (8°) and -insensitive (25°) flip angles. Clinical data were obtained from patients with malignant and benign breast tumors. Data were fitted using a 2-compartment TK model and a 1-compartment TK model combined with 4 WX models: fast exchange limit (FXL), no exchange, 2PX, and shutter-speed. RESULTS: Fits to the 1-compartment simulated data were excellent, but estimates of WX obtained using the 2PX and shutter-speed models were poor. One-compartment TK model fits to the clinical malignant tumor data were bad, except for the shutter-speed model. However, that overestimated TK parameters compared to the best-fit 2-compartment TK model, which predicted a significant blood volume and leaky capillaries (1 tracer compartment is insufficient, 2 are necessary). All models produced excellent fits to the clinical benign tumor data with little variation between parameter estimates (1 tracer compartment is sufficient). CONCLUSION: The 2PX and shutter-speed models were unable to estimate WX from the DCE-MRI data. A good fit to malignant tumor data using the shutter-speed model was not explained by WX, but the choice of an inappropriate TK model leading to distorted parameter estimates.

A functional form for a representative individual arterial input function measured from a population using high temporal resolution DCE MRI.

PURPOSE: To measure the arterial input function (AIF), an essential component of tracer kinetic analysis, in a population of patients using an optimized dynamic contrast-enhanced (DCE) imaging sequence and to estimate inter- and intrapatient variability. From these data, a representative AIF that may be used for realistic simulation studies can be extracted. METHODS: Thirty-nine female patients were imaged on multiple visits before and during a course of neoadjuvant chemotherapy for breast cancer. A total of 97 T1 -weighted DCE studies were analyzed including bookend estimates of T1 and model-fitting to each individual AIF. Area under the curve and cardiac output were estimated from each first pass peak, and these data were used to assess inter- and intrapatient variability of the AIF. RESULTS: Interpatient variability exceeded intrapatient variability of the AIF. There was no change in cardiac output as a function of MR visit (mean value 5.6 ± 1.1 L/min) but baseline blood T1 increased significantly following the start of chemotherapy (which was accompanied by a decrease in hematocrit). CONCLUSION: The AIF in an individual patient can be measured reproducibly but the variability of AIFs between patients suggests that use of a population AIF will decrease the precision of tracer kinetic analysis performed in cross-patient comparison studies. A representative AIF is presented that is typical of the population but retains the characteristics of an individually measured AIF.

Incidental significant arrhythmia in scleroderma associates with cardiac magnetic resonance measure of fibrosis and hs-TnI and NT-proBNP.

OBJECTIVES: To screen for significant arrhythmias with an implantable loop recorder (ILR) in patients with SSc and no known cardiovascular disease, and identify associated disease phenotype, blood and cardiovascular magnetic resonance (CMR) biomarkers. METHODS: Twenty patients with SSc with no history of primary SSc heart disease, traditional cardiovascular disease, diabetes or maximum one traditional cardiovascular risk factor underwent clinical assessment, contrast-enhanced CMR and ILR insertion. RESULTS: ILR data were available for 19 patients: 63% female, mean (s.d.) age of 53 (12) years, 32% diffuse SSc. Eight patients had significant arrhythmias over 3 years: one complete heart block, two non-sustained ventricular tachycardia [all three dcSSc, two anti-topoisomerase antibodies (Scl70) positive, three interstitial lung disease and two previous digital ulceration] and five atrial arrhythmias of which four were with limited SSc. These required interventions with one permanent pacemaker implantation, four anti-arrhythmic pharmacotherapy, one anticoagulation.Patients with significant arrhythmia had higher baseline high-sensitivity troponin I and N-terminal pro-brain natriuretic peptide [mean difference (95% CI) 117 (-11, 245) and 92 (-30, 215) ng/l, respectively], and CMR-extracellular volume [mean (s.d.) 32 (2) vs 29 (4)%]. Late gadolinium enhancement was observed in five patients, only one with significant arrhythmia. CONCLUSION: This first ILR study identified potentially life-threatening arrhythmias in asymptomatic SSc patients attributable to a primary SSc heart disease. Disease phenotype, CMR-extracellular volume (indicating diffuse fibrosis) and cardiac biomarkers may identify at-risk patients that would benefit from ILR screening. Future studies can inform a risk model and provide insights into SSc-associated arrhythmia pathogenesis.

Estimating breast tumor blood flow during neoadjuvant chemotherapy using interleaved high temporal and high spatial resolution MRI.

PURPOSE: To evaluate an interleaved MRI sampling strategy that acquires both high temporal resolution (HTR) dynamic contrast-enhanced (DCE) data for quantifying breast tumor blood flow (TBF) and high spatial resolution (HSR) DCE data for clinical reporting, following a single standard injection of contrast agent. METHODS: A simulation study was used to evaluate the performance of the interleaved technique under different conditions. In a prospective clinical study, 18 patients with primary breast cancer, who were due to undergo neoadjuvant chemotherapy (NACT), were examined using interleaved HTR and HSR DCE-MRI at 1.5 Tesla. Tumor regions of interest were analyzed with a two-compartment tracer kinetic model. Paired parameters (n = 10) from the data acquired before and post-cycle 2 of NACT were compared using the nonparametric Wilcoxon signed-rank test. RESULTS: Simulations demonstrated that TBF was reliably estimated using the proposed strategy. The region of interest analysis revealed significant changes in TBF (0.81-0.43 mL/min/mL; P = 0.002) following two cycles of NACT. The HSR data were reported in the normal way and enabled the assessment of tumor volume, which decreased by 53% following NACT (P = 0.065). CONCLUSIONS: TBF can be measured reliably using the proposed strategy without compromising a standard clinical protocol. Furthermore, in our feasibility study, TBF decreased significantly following NACT, whereas capillary permeability surface-area product did not. Magn Reson Med 79:317-326, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Sensitivity of quantitative myocardial dynamic contrast-enhanced MRI to saturation pulse efficiency, noise and t1 measurement error: Comparison of nonlinearity correction methods.

PURPOSE: To compare methods designed to minimize or correct signal nonlinearity in quantitative myocardial dynamic contrast-enhanced (DCE) MRI. METHODS: DCE-MRI studies were simulated and data acquired in eight volunteers. Signal nonlinearity was corrected using either a dual-bolus approach or model-based correction using proton-density weighted imaging (conventional or dual-sequence acquisition) or T1 data (native or bookend). Scanning of healthy and infarcted myocardium at 3 T was simulated, including noise, saturation imperfection and T1 measurement error. Data were analyzed using model-based deconvolution with a one-compartment (mono-exponential) model. RESULTS: Substantial variation between methods was demonstrated in volunteers. In simulations the dual-bolus method proved stable for realistic levels of saturation efficiency but demonstrated bias due to residual nonlinearity. Model-based methods performed ideally in the absence of confounding error sources and were generally robust to noise or saturation imperfection, except for native T1 based correction which was highly sensitive to the latter. All methods demonstrated large variation in accuracy above an over-saturation level where baseline signal was nulled. For the dual-sequence approach this caused substantial bias at the saturation efficiencies observed in volunteers. CONCLUSION: The choice of nonlinearity correction method in myocardial DCE-MRI impacts on accuracy and precision of estimated parameters, particularly in the presence of nonideal saturation.

Gadofosveset-based biomarker of tissue albumin concentration: Technical validation in vitro and feasibility in vivo.

PURPOSE: There is currently no adequate method of mapping physiologic and pathophysiologic tissue albumin concentrations in human subjects. The objective of this study was to devise and evaluate a biomarker of regional albumin concentration using gadofosveset-enhanced MRI. THEORY AND METHODS: A binding and relaxation model was devised and evaluated in vitro in solutions of albumin at 3.0 Tesla (T) and 4.7T. The method was evaluated in the heart in seven volunteers at 3.0T. RESULTS: MRI-derived estimates of albumin concentration were in good agreement with true values over the range 0.1-1.0 mM (Pearson correlation coefficients of 0.85 and 0.88 for 3.0T and 4.7T, respectively). The mean calculated albumin concentration in the myocardium for the volunteers was 0.02 mM (range, 0.01-0.03 mM). CONCLUSION: Accurate estimates of albumin concentration in vitro suggest this may be a viable noninvasive alternative to existing techniques. In the myocardium the MRI-derived estimates of albumin concentration indicate the practical feasibility of the technique but were below expected values. Gadofosveset-enhanced MR relaxometry has potential in providing biomarkers of regional albumin concentration; further evaluation is required before it can be used reliably in vivo.

The relationship between parameters measured using intravoxel incoherent motion and dynamic contrast-enhanced MRI in patients with breast cancer undergoing neoadjuvant chemotherapy: a longitudinal cohort study.

Purpose: The primary aim of this study was to explore whether intravoxel incoherent motion (IVIM) can offer a contrast-agent-free alternative to dynamic contrast-enhanced (DCE)-MRI for measuring breast tumor perfusion. The secondary aim was to investigate the relationship between tissue diffusion measures from DWI and DCE-MRI measures of the tissue interstitial and extracellular volume fractions. Materials and methods: A total of 108 paired DWI and DCE-MRI scans were acquired at 1.5 T from 40 patients with primary breast cancer (median age: 44.5 years) before and during neoadjuvant chemotherapy (NACT). DWI parameters included apparent diffusion coefficient (ADC), tissue diffusion (Dt), pseudo-diffusion coefficient (Dp), perfused fraction (f), and the product f×Dp (microvascular blood flow). DCE-MRI parameters included blood flow (Fb), blood volume fraction (vb), interstitial volume fraction (ve) and extracellular volume fraction (vd). All were extracted from three tumor regions of interest (whole-tumor, ADC cold-spot, and DCE-MRI hot-spot) at three MRI visits: pre-treatment, after one, and three cycles of NACT. Spearman's rank correlation was used for assessing between-subject correlations (r), while repeated measures correlation was employed to assess within-subject correlations (rrm) across visits between DWI and DCE-MRI parameters in each region. Results: No statistically significant between-subject or within-subject correlation was found between the perfusion parameters estimated by IVIM and DCE-MRI (f versus vb and f×Dp versus Fb; P=0.07-0.81). Significant moderate positive between-subject and within-subject correlations were observed between ADC and ve (r=0.461, rrm=0.597) and between Dt and ve (r=0.405, rrm=0.514) as well as moderate positive within-subject correlations between ADC and vd and between Dt and vd (rrm=0.619 and 0.564, respectively) in the whole-tumor region. Conclusion: No correlations were observed between the perfusion parameters estimated by IVIM and DCE-MRI. This may be attributed to imprecise estimates of fxDp and vb, or an underlying difference in what IVIM and DCE-MRI measure. Care should be taken when interpreting the IVIM parameters (f and f×Dp) as surrogates for those measured using DCE-MRI. However, the moderate positive correlations found between ADC and Dt and the DCE-MRI parameters ve and vd confirms the expectation that as the interstitial and extracellular volume fractions increase, water diffusion increases.

Prediction and assessment of responses to renal artery revascularization with dynamic contrast-enhanced magnetic resonance imaging: a pilot study.

The aim of this study was to assess the potential of dynamic contrast-enhanced (DCE) MRI to predict and evaluate functional outcomes after renal artery revascularization for renal artery stenosis (RAS). The single-kidney glomerular filtration rate (SK-GFR) was measured in 15 patients with atherosclerotic RAS with DCE-MRI and radioisotopes at baseline and 4 mo after revascularization. DCE-MRI also produced measurements of blood flow, blood volume, extraction fraction, tubular transit time, and functional volume. Stented kidneys (n = 22) were divided into three response groups on the basis of the changes in radioisotope SK-GFR: improved (n = 5), stable (n = 13), and deteriorated (n = 4). A good agreement was found between SK-GFR values from DCE-MRI and radioisotopes (correlation coefficient: 0.91). Before intervention, kidneys that improved had lower extraction fraction, higher blood volume, longer tubular transit time, and lower SK-GFR. After intervention, improved kidneys had increased functional volume, and deteriorated kidneys had reduced functional volume and extraction fraction. Revascularization improved blood flow and blood volume in all groups. This pilot study led to the hypothesis that well-vascularized kidneys with reduced extraction fractions are most likely to benefit from revascularization. More generally, DCE-MRI has the potential to replace radioisotope measurement of SK-GFR and may improve patient management by providing additional information on tissue perfusion.

Myocardial blood flow at rest and stress measured with dynamic contrast-enhanced MRI: comparison of a distributed parameter model with a Fermi function model.

PURPOSE: To assess the feasibility of simultaneously measuring blood flow (Fb ), Gd-DTPA extraction fraction (E), and distribution volume (vd ) in healthy myocardium at rest and under adenosine stress using dynamic contrast-enhanced MRI. METHODS: Sixteen volunteers were examined at 1.5 T and 11 returned for a repeat study. The data were analyzed using a distributed parameter (DP) 2-region model to arrive at estimates of Fb , E, blood volume, and interstitial volume. For comparison, estimates of Fb were also obtained using a Fermi function model. RESULTS: DP model fits were successful in 49 of the 54 data sets. Estimates obtained using DP and Fermi models did not differ for either rest Fb or myocardial perfusion reserve though DP estimates of stress Fb were lower than Fermi estimates. The repeatability of the DP parameters Fb , E, and vd was better than or equal to the repeatability of Fermi-Fb . E at rest and under stress was estimated to be 66% and 57%, respectively. CONCLUSION: The results suggest that characteristics of the microvasculature of healthy myocardium can be reliably determined using dynamic contrast-enhanced MRI at rest and under stress and that delivery of Gd-DTPA to the myocardium is not flow-limited.

Classic models for dynamic contrast-enhanced MRI.

Dynamic contrast-enhanced MRI (DCE-MRI) is a functional MRI method where T1 -weighted MR images are acquired dynamically after bolus injection of a contrast agent. The data can be interpreted in terms of physiological tissue characteristics by applying the principles of tracer-kinetic modelling. In the brain, DCE-MRI enables measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), blood-brain barrier (BBB) permeability-surface area product (PS) and the volume of the interstitium (ve ). These parameters can be combined to form others such as the volume-transfer constant K(trans) , the extraction fraction E and the contrast-agent mean transit times through the intra- and extravascular spaces. A first generation of tracer-kinetic models for DCE-MRI was developed in the early 1990s and has become a standard in many applications. Subsequent improvements in DCE-MRI data quality have driven the development of a second generation of more complex models. They are increasingly used, but it is not always clear how they relate to the models of the first generation or to the model-free deconvolution methods for tissues with intact BBB. This lack of understanding is leading to increasing confusion on when to use which model and how to interpret the parameters. The purpose of this review is to clarify the relation between models of the first and second generations and between model-based and model-free methods. All quantities are defined using a generic terminology to ensure the widest possible scope and to reveal the link between applications in the brain and in other organs.

First-in-human technique translation of oxygen-enhanced MRI to an MR Linac system in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Tumour hypoxia is prognostic in head and neck cancer (HNC), associated with poor loco-regional control, poor survival and treatment resistance. The advent of hybrid MRI - radiotherapy linear accelerator or 'MR Linac' systems - could permit imaging for treatment adaptation based on hypoxic status. We sought to develop oxygen-enhanced MRI (OE-MRI) in HNC and translate the technique onto an MR Linac system. MATERIALS AND METHODS: MRI sequences were developed in phantoms and 15 healthy participants. Next, 14 HNC patients (with 21 primary or local nodal tumours) were evaluated. Baseline tissue longitudinal relaxation time (T1) was measured alongside the change in 1/T1 (termed ΔR1) between air and oxygen gas breathing phases. We compared results from 1.5 T diagnostic MR and MR Linac systems. RESULTS: Baseline T1 had excellent repeatability in phantoms, healthy participants and patients on both systems. Cohort nasal concha oxygen-induced ΔR1 significantly increased (p < 0.0001) in healthy participants demonstrating OE-MRI feasibility. ΔR1 repeatability coefficients (RC) were 0.023-0.040 s-1 across both MR systems. The tumour ΔR1 RC was 0.013 s-1 and the within-subject coefficient of variation (wCV) was 25% on the diagnostic MR. Tumour ΔR1 RC was 0.020 s-1 and wCV was 33% on the MR Linac. ΔR1 magnitude and time-course trends were similar on both systems. CONCLUSION: We demonstrate first-in-human translation of volumetric, dynamic OE-MRI onto an MR Linac system, yielding repeatable hypoxia biomarkers. Data were equivalent on the diagnostic MR and MR Linac systems. OE-MRI has potential to guide future clinical trials of biology guided adaptive radiotherapy.

BOLD imaging: a potential predictive biomarker of renal functional outcome following revascularization in atheromatous renovascular disease.

BACKGROUND: Stenting of the stenosed renal artery is commonly employed in atheromatous renovascular disease (ARVD) in order to revascularize the affected kidney. However, it is still far from clear which patient subgroups should be revascularized as stenting carries small but significant risks. We have previously demonstrated that the ratio of magnetic resonance-measured renal volume to isotopic single kidney glomerular filtration rate (isoSK-GFR) is higher in kidneys which show functional improvement after revascularization. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) does not require contrast administration and is sensitive to changes in tissue concentration of deoxyhaemoglobin. METHODS: In this study, we test the hypothesis that baseline BOLD R2* map signal and R2*:isoSK-GFR ratio will provide an additional independent predictive biomarker of response to revascularization. RESULTS: Studies were performed in 28 subjects (16 ARVD and 12 controls). All subjects had R2* mapping and isoSK-GFR measured at baseline and at 4-month follow-up. MRI data were collected on a 3 T whole-body MRI scanner using a coronal dual-echo, 2D gradient-echo breath-hold acquisition. Parenchymal regions of interest (ROIs) were drawn on a representative slice through the middle of the kidney. Parametric maps of R2* were generated and mean values of R2* were calculated for every ROI. The ratio of R2*:isoSK-GFR at baseline was significantly greater in kidneys where renal function improved (5.91 ± 6.51) versus stable (1.78 ± 1.11), deteriorated (2.15 ± 1.79) or controls (1.5 ± 0.91), P = 0.003. R2*:isoSK-GFR ratio that was greater than 95% confidence interval of the control kidneys was 66.7% sensitive, but 85.7% specific in predicting a positive renal functional outcome. CONCLUSIONS: These pilot data show that BOLD R2* imaging, presumably by detecting intra-renal deoxyhaemoglobin in still viable 'hibernating' parenchyma, coupled with isoSK-GFR may provide an effective predictive biomarker for positive renal functional response to revascularization. R2* imaging is non-invasive, quick to perform and could provide further insight into reversible parenchymal changes in ARVD kidneys.