Quantification of Cerebral Glucose Concentrations via Detection of the H1-α-Glucose Peak in 1 H MRS at 7 T.

BACKGROUND: Sensitive detection and quantification of cerebral glucose is desired. PURPOSE: To quantify cerebral glucose by detecting the H1-α-glucose peak at 5.23 ppm in 1 H magnetic resonance spectroscopy at 7 T. STUDY TYPE: Prospective. SUBJECTS: Twenty-eight non-fasted healthy subjects (aged 20-28 years). FIELD STRENGTH/SEQUENCE: Short echo time stimulated echo acquisition mode (short-TE STEAM) and semi-localized by adiabatic selective refocusing (semi-LASER) at 7 T. ASSESSMENT: Single voxel spectra were obtained from the posterior cingulate cortex (27-mL) using a 32-channel head coil. The H1-α-glucose peak in the spectrum with retrospective removal of the residual water peak was fitted using LCModel with a glucose basis set of only the H1-α-glucose peak. Conventional spectral analysis was performed with a glucose basis set of a full spectral pattern of glucose, also. Fitting precision was evaluated with Cramér-Rao lower bounds (CRLBs). The repeatability of glucose quantification via the semi-LASER sequence was tested. STATISTICAL TESTS: Paired or Welch's t-test were used for normally distributed values. A P value of <0.05 was considered significant. The repeatability of measures was analyzed using coefficient of variation (CV). RESULTS: Removal of the residual water peak improved the flatness and stability of baselines around the H1-α-glucose peak and reduced CRLBs for fitting the H1-α-glucose peak. The semi-LASER sequence was superior to the short-TE STEAM in the higher signal-to-noise ratio of the H1-α-glucose peak (mean ± SD 7.9 ± 2.5, P < 0.001). The conventional analysis overfitted the H1-α-glucose peak. The individual CVs of glucose quantification by detecting the H1-α-glucose peak were smaller than the corresponding CRLBs. DATA CONCLUSION: Cerebral glucose concentration is quantitated to be 1.07 mM by detecting the H1-α-glucose peak in the semi-LASER spectra. Despite requiring long scan times, detecting the H1-α-glucose peak allows true glucose quantification free from the influence of overlapping taurine and macromolecule signals. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1.

GABA, glutamate and excitatory-inhibitory ratios measured using short-TE STEAM MRS at 7-Tesla: Effects of macromolecule basis sets and baseline parameters.

Rationale and objectives: Macromolecules (MMs) affect the precision and accuracy of neurochemical quantification in magnetic resonance spectroscopy. A measured MM basis is increasingly used in LCModel analysis combined with a spline baseline, whose stiffness is controlled by a parameter named DKNTMN. The effects of measured MM basis and DKNTMN were investigated. Materials and methods: Twenty-six healthy subjects were prospectively enrolled and scanned twice using a short echo-time Stimulated Echo Acquisition Mode (STEAM) at 7-T. Using LCModel, analyses were conducted using the simulated MM basis (MMsim) with DKNTMN 0.15 and an MM basis measured inhouse (MMmeas) with DKNTMN of 0.15, 0.30, 0.60 and 1.00. Cramér-Rao lower bound (CRLB) and the concentrations of gamma-aminobutyric acid (GABA), glutamate and excitatory-inhibitory ratio (EIR), in addition to MMs were statistically analyzed. Measurement stability was evaluated using coefficient of variation (CV). Results: CRLBs of GABA were significantly lower when using MMsim than MMmeas; those of glutamate were 2-3. GABA concentrations were significantly higher in the analysis using MMsim than MMmeas where concentrations were significantly higher with DKNTMN of 0.15 or 0.30 than 0.60 or 1.00. Difference in glutamate concentration was not significant. EIRs showed the same difference as in GABA depending on the DKNTMN values. CVs between test-retest scans were relatively stable for glutamate but became larger as DKNTMN increased for GABA and EIR. Conclusion: Neurochemical quantification depends on the parameters of the basis sets used for fitting. Analysis using MMmeas with DKNTMN of 0.30 conformed best to previous studies and is recommended.

Simultaneous multislice diffusion-weighted imaging versus standard diffusion-weighted imaging in whole-body PET/MRI.

OBJECTIVE: To compare standard (STD-DWI) single-shot echo-planar imaging DWI and simultaneous multislice (SMS) DWI during whole-body positron emission tomography (PET)/MRI regarding acquisition time, image quality, and lesion detection. METHODS: Eighty-three adults (47 females, 57%), median age of 64 years (IQR 52-71), were prospectively enrolled from August 2018 to March 2020. Inclusion criteria were (a) abdominal or pelvic tumors and (b) PET/MRI referral from a clinician. Patients were excluded if whole-body acquisition of STD-DWI and SMS-DWI sequences was not completed. The evaluated sequences were axial STD-DWI at b-values 50-400-800 s/mm2 and the apparent diffusion coefficient (ADC), and axial SMS-DWI at b-values 50-300-800 s/mm2 and ADC, acquired with a 3-T PET/MRI scanner. Three radiologists rated each sequence's quality on a five-point scale. Lesion detection was quantified using the anatomic MRI sequences and PET as the reference standard. Regression models were constructed to quantify the association between all imaging outcomes/scores and sequence type. RESULTS: The median whole-body STD-DWI acquisition time was 14.8 min (IQR 14.1-16.0) versus 7.0 min (IQR 6.7-7.2) for whole-body SMS-DWI, p < 0.001. SMS-DWI image quality scores were higher than STD-DWI in the abdomen (OR 5.31, 95% CI 2.76-10.22, p < 0.001), but lower in the cervicothoracic junction (OR 0.21, 95% CI 0.10-0.43, p < 0.001). There was no significant difference in the chest, mediastinum, pelvis, and rectum. STD-DWI detected 276/352 (78%) lesions while SMS-DWI located 296/352 (84%, OR 1.46, 95% CI 1.02-2.07, p = 0.038). CONCLUSIONS: In cancer staging and restaging, SMS-DWI abbreviates acquisition while maintaining or improving the diagnostic yield in most anatomic regions. KEY POINTS: • Simultaneous multislice diffusion-weighted imaging enables faster whole-body image acquisition. • Simultaneous multislice diffusion-weighted imaging maintains or improves image quality when compared to single-shot echo-planar diffusion-weighted imaging in most anatomical regions. • Simultaneous multislice diffusion-weighted imaging leads to superior lesion detection.

Repeatability of proton magnetic resonance spectroscopy of the brain at 7 T: effect of scan time on semi-localized by adiabatic selective refocusing and short-echo time stimulated echo acquisition mode scans and their comparison.

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) provides a unique opportunity for in vivo measurements of the brain's metabolic profile. Two methods of mainstream data acquisition are compared at 7 T, which provides certain advantages as well as challenges. The two representative methods have seldom been compared in terms of measured metabolite concentrations and different scan times. The current study investigated proton MRS of the posterior cingulate cortex using a semi-localized by adiabatic selective refocusing (sLASER) sequence and a short echo time (TE) stimulated echo acquisition mode (sSTEAM) sequence, and it compared their reliability and repeatability at 7 T using a 32-channel head coil. METHODS: Sixteen healthy subjects were prospectively enrolled and scanned twice with an off-bed interval between scans. The scan parameters for sLASER were a TR/TE of 6.5 s/32 ms and 32 and 48 averages (sLASER×32 and sLASER×48, respectively). The scan parameters for sSTEAM were a TR/TE of 4 s/5 ms and 32, 48, and 64 averages (sSTEAM4×32, sSTEAM4×48, and sSTEAM4×64, respectively) in addition to that with a TR/TE of 8 s/5 ms and 32 averages (sSTEAM8×32). Data were analyzed using LCModel. Metabolites quantified with Cramér-Rao lower bounds (CRLBs) >50% were classified as not detected, and metabolites quantified with mean or median CRLBs ≤20% were included for further analysis. The SNR, CRLBs, coefficient of variation (CV), and metabolite concentrations were statistically compared using the Shapiro-Wilk test, one-way ANOVA, or the Friedman test. RESULTS: The sLASER spectra for N-acetylaspartate + N-acetylaspartylglutamate (tNAA) and glutamate (Glu) had a comparable or higher SNR than sSTEAM spectra. Ten metabolites had lower CRLBs than prefixed thresholds: aspartate (Asp), γ-aminobutyric acid (GABA), glutamine (Gln), Glu, glutathione (GSH), myo-inositol (Ins), taurine (Tau), the total amount of phosphocholine + glycerophosphocholine (tCho), creatine + phosphocreatine (tCr), and tNAA. Performance of the two sequences was satisfactory except for GABA, for which sLASER yielded higher CRLBs (≥18%) than sSTEAM. Some significant differences in CRLBs were noted, but they were ≤2% except for GABA and Gln. Signal averaging significantly lowered CRLBs for some metabolites but only by a small amount. Measurement repeatability as indicated by median CVs was ≤10% for Gln, Glu, Ins, tCho, tCr, and tNAA in all scans, and that for Asp, GABA, GSH, and Tau was ≥10% under some scanning conditions. The CV for GABA according to sLASER was significantly higher than that according to sSTEAM, whereas the CV for Ins was higher according to sSTEAM. An increase in signal averaging contribute little to lower CVs except for Ins. CONCLUSIONS: Both sequences quantified brain metabolites with a high degree of precision and repeatability. They are comparable except for GABA, for which sSTEAM would be a better choice.

Comparison of Functional Free-Breathing Pulmonary 1H and Hyperpolarized 129Xe Magnetic Resonance Imaging in Pediatric Cystic Fibrosis.

RATIONALE AND OBJECTIVES: Phase resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is a free-breathing 1H-based technique that produces maps of fractional ventilation (FV). This study compared ventilation defect percent (VDP) calculated using PREFUL to hyperpolarized (HP) 129Xe MRI and pulmonary function tests in pediatric cystic fibrosis (CF). MATERIALS AND METHODS: 27 pediatric participants were recruited (mean age 13.0 ± 2.7), including 6 with clinically stable CF, 11 CF patients undergoing a pulmonary exacerbation (PEx), and 10 healthy controls. Spirometry was performed to measure forced expiratory volume in 1 second (FEV1), along with nitrogen multiple breath washout to measure lung clearance index (LCI). VDP was calculated from single central coronal slice PREFUL FV maps and the corresponding HP 129Xe slice. RESULTS: The stable CF group had a normal FEV1 (p = 0.41) and elevated LCI (p = 0.007). The CF PEx group had a decreased FEV1 (p < 0.0001) and elevated LCI (p < 0.0001). PREFUL and HP 129Xe VDP were significantly different between the CF PEx and healthy groups (p < 0.05). In the stable CF group, PREFUL and HP 129Xe VDP were not significantly different from the healthy group (p = 0.18 and 0.08, respectively). There was a correlation between PREFUL and HP 129Xe VDP (R2 = 0.31, p = 0.004), and both parameters were significantly correlated with FEV1 and LCI. CONCLUSION: PREFUL MRI is feasible in pediatric CF, distinguishes patients undergoing pulmonary exacerbations compared to healthy subjects, and correlates with HP 129Xe MRI as well as functional measures of disease severity. PREFUL MRI does not require breath-holds and is straight forward to implement on any MRI scanner.

Image quality and diagnostic accuracy of complex-averaged high b value images in diffusion-weighted MRI of prostate cancer.

PURPOSE: To evaluate the impact of complex-averaging on image quality (IQ) and diagnostic accuracy of acquired and calculated high b value (aHBV, cHBV) images in diffusion-weighted prostate MRI. MATERIALS AND METHODS: This retrospective study included 84 patients who underwent multiparametric prostate MRI at 3 Tesla without endorectal coil. DWIs were acquired at three different b values which included two lower b values (b = 50,900 s/mm2) and one higher b value (aHBV at 2000 s/mm2). The acquired data were postprocessed to generate two different types of trace-weighted images-using conventional magnitude-averaging and complex-averaging. Using lower b values (b = 50,900 s/mm2) from both conventional and complex-averaged image sets, cHBV images (b = 2000 s/mm2) and ADC maps were derived. All image sets were reviewed by two radiologists in different reading sessions to assess image quality and PIRADS. The diagnostic accuracy of different image sets for the detection of prostate lesions was performed by correlating PIRADS and Gleason scores. RESULTS: Complex-averaging did not impact ADC values of the prostate lesions compared to magnitude-averaging (P = 0.08). Complex-averaging improved image quality of acquired high b value and calculated high b value images (P < 0.0001). Complex-averaging also improved the level of confidence (LOC) of the acquired high b value for both readers (P < 0.0001, P < 0.05), but only for reader A in calculated high b value (P < 0.0001). The image quality of calculated high b value images was not significantly different than acquired high b value images. The dataset combining complex-averaging and calculated high b value provided the highest diagnostic accuracy (but not statistically significant) for detection of the significant prostate lesion compared to the magnitude-averaged acquired high b value (79.55% vs. 72.73%; P = 0.317). The mean acquisition time for b = 2000 s/mm2 sequence (aHBV) was 6 min 30 s (± 1 min 16 s) out of a total of 28 min 31 s (± 4 min 26 s) for the entire mp-MRI protocol (approximately 25% of total scan time). CONCLUSION: Complex-averaging provides better image quality and level of confidence without significant impact on ADC values and diagnostic accuracy for detection of the significant prostate lesions . The calculated high b value images are also comparable to (and can substitute) the acquired high b value images which can help in reducing the imaging time.

Language universals engage Broca's area.

It is well known that natural languages share certain aspects of their design. For example, across languages, syllables like blif are preferred to lbif. But whether language universals are myths or mentally active constraints-linguistic or otherwise-remains controversial. To address this question, we used fMRI to investigate brain response to four syllable types, arrayed on their linguistic well-formedness (e.g., blif≻bnif≻bdif≻lbif, where ≻ indicates preference). Results showed that syllable structure monotonically modulated hemodynamic response in Broca's area, and its pattern mirrored participants' behavioral preferences. In contrast, ill-formed syllables did not systematically tax sensorimotor regions-while such syllables engaged primary auditory cortex, they tended to deactivate (rather than engage) articulatory motor regions. The convergence between the cross-linguistic preferences and English participants' hemodynamic and behavioral responses is remarkable given that most of these syllables are unattested in their language. We conclude that human brains encode broad restrictions on syllable structure.

Validation of catheter segmentation for MR-guided gynecologic cancer brachytherapy.

Segmentation of interstitial catheters from MRI needs to be addressed in order for MRI-based brachytherapy treatment planning to become part of the clinical practice of gynecologic cancer radiotherapy. This paper presents a validation study of a novel image-processing method for catheter segmentation. The method extends the distal catheter tip, interactively provided by the physician, to its proximal end, using knowledge of catheter geometry and appearance in MRI sequences. The validation study consisted of comparison of the algorithm results to expert manual segmentations, first on images of a phantom, and then on patient MRI images obtained during MRI-guided insertion of brachytherapy catheters for the treatment of gynecologic cancer. In the phantom experiment, the maximum disagreement between automatic and manual segmentation of the same MRI image, as computed using the Hausdorf distance, was 1.5 mm, which is of the same order as the MR image spatial resolution, while the disagreement between automatic segmentation of MR images and "ground truth", manual segmentation of CT images, was 3.5 mm. The segmentation method was applied to an IRB-approved retrospective database of 10 interstitial brachytherapy patients which included a total of 101 catheters. Compared with manual expert segmentations, the automatic method correctly segmented 93 out of 101 catheters, at an average rate of 0.3 seconds per catheter using a 3 GHz Intel Core i7 computer with 16 GB RAM and running Mac OS X 10.7. These results suggest that the proposed catheter segmentation is both technically and clinically feasible.

Analysis of myocardial perfusion MRI.

Rapid MR imaging (MRI) during the first pass of an injected tracer is used to assess myocardial perfusion with a spatial resolution of 2-3 mm, and to detect any regional impairments of myocardial blood flow (MBF) that may lead to ischemia. The spatial resolution is sufficient to detect flow reductions that are limited to the subendocardial layer. The capacity of the coronary system to increase MBF severalfold in response to vasodilation can be quantified by analysis of the myocardial contrast enhancement. The myocardial perfusion reserve (MPR) is a useful concept for quantifying the vasodilator response. The perfusion reserve can be estimated from the ratio of MBFs during vasodilation and at baseline, in units identical to those used for invasive measurements with labeled microspheres, or from dimensionless flow indices normalized by their value for autoregulated flow at rest. The perfusion reserve can be reduced as a result of a blunted hyperemic response and/or an abnormal resting blood flow. The absolute quantification of MBF removes uncertainties in the evaluation of the vasodilator response, and can be achieved without the use of complex tracer kinetic models; therefore, its application to clinical studies is feasible.

Applications of magnetic resonance imaging for cardiac stem cell therapy.

BACKGROUND: The latest generation of interactive cardiac magnetic resonance (MR) scanners has made cardiac interventions with real-time MRI possible. To date, cardiac MRI has been mostly applied to measure myocardial perfusion, viability, and regional function, but now the application of cardiac MRI can be extended to cardiovascular interventions. The purpose of this article is to illustrate the potential of MRI in stem cell therapy for cardiac restoration. METHODS: We have applied MRI to (1) interactively target myocardial injections with a novel stem cell delivery catheter, and to compare gadolinium/blue dye injections to pathology; (2) assess myocardial perfusion with MR first pass imaging in an infarct model treated with stem cell therapy versus control animals; (3) measure regional functional changes using myocardial tissue tagging in the same animals. RESULTS: We were able to demonstrate the feasibility and safety of myocardial injections under MR fluoroscopy. The intramyocardial distribution of the blue dye at necropsy correlated well with the extent of gadolinium, as detected with a three-dimensional inversion recovery MR pulse sequence for late enhancement immediately after contrast injection. Preliminary results show that myocardial perfusion reserve and regional wall motion improved in the stem-cell-treated group, compared to a control group. CONCLUSIONS: These preliminary results suggest that (1) injections into the LV myocardium can be performed under real-time MRI guidance using a directed catheter approach, and (2) regional myocardial perfusion and function, measured with MRI, both improve after stem cell therapy. This ongoing study demonstrates the potential of MRI for image-guided interventions, combined with detailed evaluation of anatomy, function, perfusion, and viability.

An approach to the three-dimensional display of left ventricular function and viability using MRI.

Cardiac MRI was performed in human volunteers to determine the magnitude of the misregistration (MSR) of cardiac landmarks due to variability in the diaphragm position for repeated breath-holds. Seven normal volunteers underwent MR imaging of the left ventricle (LV) to evaluate the magnitude of the endocardial centroid MSR. The MSR for a mid-ventricle short-axis image was 3.01 +/- 1.68 mm through-plane and 4.16 +/- 1.62 mm in-plane. A second order polynomial fit through the LV centroid coordinates minimized the in-plane component of the MSR error. Short-axis cine images, corrected for MSR, provided high-resolution 2D data from which an accurate anatomical model of the LV was generated. Anatomical landmarks were used to register parametric maps of myocardial perfusion and viability to the three-dimensional (3D) model, with the corresponding parameters displayed as color-encoded values on the endo- and epicardial surfaces of the LV. Registration of regional wall motion, perfusion and viability to the 3D model was performed for three patients with a history of cardiovascular disease. The proposed 3D reconstruction technique allows visualization in 3D of the LV anatomy, in combination with parametric mapping of its functional status.

Magnetic resonance imaging guided cardiovascular interventions in congenital heart diseases.

The purpose of this article is to present some recent applications of diagnostic and interventional MRI in congenital heart disease. To date x-ray-based techniques have been the norm for most diagnostic and therapeutic applications. With the advent of ultrafast MRI and the development of MRI-compatible catheters and guide wires, the goal of achieving real-time guidance by MRI for interventions in congenital heart diseases has proven feasible. We briefly review the latest advances in cardiovascular MRI, and the development of MR-compatible devices for diagnostic and therapeutic applications such as ASD closure and pulmonary artery dilation.

Feedback-assisted three-dimensional reconstruction of the left ventricle with MRI.

PURPOSE: To develop and test a new technique for rapid, accurate three-dimensional (3D) reconstruction of the left ventricle (LV) and calculation of its volume parameters, with images from multiple orientations and interactive feedback. MATERIALS AND METHODS: The ventricular surface was fit to a number of user-placed guide points in magnetic resonance (MR) images using bivariate smoothing splines. A 3D model was reconstructed and the LV volumes were calculated at both end diastole (ED) and end systole (ES). This technique was validated using a phantom, and applied to studies of 18 patients and four volunteers (N = 22) imaged on a 1.5-T clinical scanner. The results of the 3D method were compared to the standard 2D short-axis slice summation technique, which is widely used for the analysis of cardiac function. RESULTS: There was excellent agreement between the computed volume of the phantom using the 3D modeling method and the actual volume (190.50 mL +/- 3.06 mL, and 191.0 mL +/- 2.5 mL, respectively). There was good correlation between the volumes calculated with our 3D model and the slice summation technique (ED volume (EDV) difference, 6.36% +/- 8.99% [mean +/- SD]; ES volume (ESV), 0.92% +/- 14.75%; stroke volume (SV), 10.54% +/- 13.95%; ejection fraction (EF), 4.22% +/- 9.16%). The 3D method was found to be more accurate than the slice summation technique for calculating LV volumes and mass from images of different slice orientations. Variations in the parameters between the two separate orientations using the 3D model vs. the slice summation method were as follows: EDV: 2.11% +/- 1.52% vs. 10.36% +/- 9.33%; ES volume: 2.76% +/- 1.64% vs. 6.39% +/- 3.62%; SV, 3.02% +/- 4.38% vs. 18.84% +/- 15.30%; EF, 2.03% +/- 2.16% vs. 8.58% +/- 6.73%; and LV mass: 4.77% +/- 2.41% vs. 24.59% +/- 6.41%. Differences in the ES volume due to the inclusion or exclusion of the most basal slice were found to be lower with the 3D model (6.90% +/- 3.83%) compared to the slice summation method (25.04% +/- 6.15%). CONCLUSION: 3D models can be used to accurately determine ventricular volume parameters. Results can be obtained using images from a variety of orientations, providing greater flexibility during image acquisition and possibly reducing the number of images needed for analysis. Feedback is provided to assist the analysis by providing a continuous update of the LV shape and volume. This feature allows the user to determine LV parameters to a predefined accuracy or to terminate the analysis when the parameters are not changing. This method is not restricted to multislice cine imaging in a single or prescribed slice orientation, and can be used for quick, accurate, and interactive analysis of cardiac function.

Magnetic resonance image-guided transcatheter closure of atrial septal defects.

BACKGROUND: Recent developments in cardiac MRI have extended the potential spectrum of diagnostic and interventional applications. The purpose of this study was to test the ability of MRI to perform transcatheter closures of secundum type atrial septal defects (ASD) and to assess ASD size and changes in right cardiac chamber volumes in the same investigation. METHODS AND RESULTS: In 7 domestic swine (body weight, 38+/-13 kg), an ASD (Q(p):Q(s)=1.7+/-0.2) was created percutaneously by balloon dilation of the fossa ovalis. The ASD was imaged and sized by both conventional radiography and MRI. High-resolution MRI of the ASD diameters correlated well with postmortem examination (r=0.97). Under real-time MR fluoroscopy, the introducer sheath was tracked toward the left atrium with the use of novel miniature MR guide wires. The defect was then closed with an Amplatzer Septal Occluder. In all animals, it was possible to track and interactively control the position of the guide wire within the vessels and the heart, including the successful deployment of the Amplatzer Septal Occluder. Right atrial and ventricular volumes were calculated before and after the intervention by using cine-MRI. Both volumes were found to be significantly reduced after ASD closure (P<0.005). CONCLUSIONS: These in vivo studies demonstrate that catheter tracking and ASD device closure can be performed under real-time MRI guidance with the use of intravascular antenna guide wires. High-resolution imaging allows accurate determination of ASD size before the intervention, and immediate treatment effects such as changes in right cardiac volumes can also be measured.

Myocardial blood flow quantification with MRI by model-independent deconvolution.

Magnetic resonance (MR) imaging during the first pass of an injected contrast agent has been used to assess myocardial perfusion, but the quantification of blood flow has been generally judged as too complex for its clinical application. This study demonstrates the feasibility of applying model-independent deconvolution to the measured tissue residue curves to quantify myocardial perfusion. Model-independent approaches only require minimal user interaction or expertise in modeling. Monte Carlo simulations were performed with contrast-to-noise ratios typical of MR myocardial perfusion studies to determine the accuracy of the resulting blood flow estimates. With a B-spline representation of the tissue impulse response and Tikhonov regularization, the bias of blood flow estimates obtained by model-independent deconvolution was less than 1% in all cases for peak contrast to noise ratios in the range from 15:1 to 20:1. The relative dispersion of blood flow estimates in Monte Carlo simulations was less than 7%. Comparison of MR blood flow estimates against measurements with radio-isotope labeled microspheres indicated excellent linear correlation (R2 = 0.995, slope: 0.96, intercept: 0.06). It can be concluded from these studies that the application of myocardial blood flow quantification with MRI can be performed with model-independent methods, and this should support a more widespread use of blood flow quantification in the clinical environment.