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Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and the progressive form of this condition, nonalcoholic steatohepatitis (NASH), has become one of the leading indications for liver transplantation. Despite intensive investigations, there are currently no United States Food and Drug Administration-approved therapies for treating NASH. A major barrier for drug development in NASH is that treatment response assessment continues to require liver biopsy, which is invasive and interpreted subjectively. Therefore, there is a major unmet need for developing noninvasive, objective, and quantitative biomarkers for diagnosis and assessment of treatment response. Emerging data support the use of magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) as a noninvasive, quantitative, and accurate measure of liver fat content to assess treatment response in early-phase NASH trials. In this review, we discuss the role and utility, including potential sample size reduction, of MRI-PDFF as a quantitative and noninvasive imaging-based biomarker in early-phase NASH trials. Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide.() NAFLD can be broadly classified into two categories: nonalcoholic fatty liver, which has a minimal risk of progression to cirrhosis, and nonalcoholic steatohepatitis (NASH), the more progressive form of NAFLD, which has a significantly increased risk of progression to cirrhosis.() Over the past two decades, NASH-related cirrhosis has become the second leading indication for liver transplantation in the United States.() For these reasons, pharmacological therapy for NASH is needed urgently. Despite intensive investigations, there are currently no therapies for treating NASH that have been approved by the United States Food and Drug Administration.().

Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the proton density fat-fraction (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction, and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5 Tesla in 13 explanted human livers. We performed colocalized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n = 117) and tissue wedges for biochemical triglyceride extraction (n = 117), and five core biopsies performed in each segment for histologic grading (n = 585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction, and histology. Intraobserver agreement, interobserver agreement, and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r = 0.984, confidence interval 0.978-0.989) and strong correlation with histology (r = 0.850, confidence interval 0.791-0.894) and triglyceride extraction (r = 0.871, confidence interval 0.818-0.909). Intraobserver agreement, interobserver agreement, and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all P

The magnetic resonance imaging–estimated proton density fat fraction (MRI-PDFF) is a novel imaging-based biomarker that allows fat mapping of the entire liver, whereas the magnetic resonance spectroscopy–measured proton density fat fraction (MRS-PDFF) provides a biochemical measure of liver fat in small regions of interest. Cross-sectional studies have shown that MRI-PDFF correlates with MRS-PDFF. The aim of this study was to show the utility of MRI-PDFF in assessing quantitative changes in liver fat through a three-way comparison of MRI-PDFF and MRS-PDFF with the liver histology–determined steatosis grade at two time points in patients with nonalcoholic fatty liver disease (NAFLD). Fifty patients with biopsy-proven NAFLD who participated in a randomized trial underwent a paired evaluation with liver biopsy, MRI-PDFF, and MRS-PDFF at the baseline and 24 weeks. The mean age and body mass index were 47.8 ± 11.7 years and 30.7 ± 6.5 kg/m2, respectively. MRI-PDFF showed a robust correlation with MRS-PDFF both at week 0 and at week 24 (r = 0.98, P < 0.0001 for both). Cross-sectionally, MRI-PDFF and MRS-PDFF increased with increases in the histology-determined steatosis grade both at week 0 and at week 24 (P < 0.05 for all). Longitudinally, patients who had a decrease (≥1%) or increase (≥1%) in MRI-PDFF (confirmed by MRS-PDFF) showed a parallel decrease or increase in their body weight and serum alanine aminotransferase and aspartate aminotransferase levels at week 24 (P < 0.05). This small increase or decrease in liver fat could not be quantified with histology.

OBJECTIVES We sought to evaluate the impact of 3.0 T on accelerated CINE steady-state free precession (SSFP) regarding signal parameters and its volumetric accuracy. MATERIAL AND METHODS Ten individuals underwent cardiac CINE imaging at 1.5 T and 3.0 T using standard single-slice CINE and multislice TSENSE-accelerated CINE (5 slices/breath-hold) with 4-fold acceleration. Data were evaluated for left ventricular volumetric parameters (EDV, ESV, and EF) as well as for SNR and CNR. Phantom based data allowed for g-factor evaluation for estimation of noise levels for accelerated data sets. Volumetric results and signal parameters were compared with results of single-slice CINE SSFP at 1.5 T as standard of reference (SOR). RESULTS Single-slice CINE at 3.0 T showed a approximately 90% increase in CNR compared with the SOR (P < 0.001). At 3.0 T, TSENSE CINE showed a less pronounced estimated loss in CNR (-58 +/- 6%) compared with single-slice CINE than at 1.5 T (-71 +/- 2%). 3.0 T TSENSE CINE showed a 21 +/- 18% lower CNR than the nonaccelerated 1.5 T CINE (P < 0.05). EF results for all data sets did not show any significant error while for EDV some errors have been encountered. CONCLUSION 3.0 T permits compensation for the high CNR loss, which accompanies the 4-fold TSENSE acceleration at 1.5 T and shows volumetric accuracy. The use of parallel imaging may help to alleviate SAR limitations at higher field strength.

Purpose The aim of the current study was to show if contrast-to-noise ratio (CNR) could be improved without loss of diagnostic accuracy if a phase-sensitive inversion recovery (PSIR) single-shot TrueFISP sequence is used at 3.0 T instead of 1.5 T. Material and methods Ten patients with myocardial infarction were examined on a 1.5 T magnetic resonance (MR) system (Avanto, Siemens Medical Systems) and at a 3.0 T MR system. Imaging delayed contrast enhancement was started 10 minutes after application of contrast material. A phase-sensitive inversion recovery (PSIR) single-shot TrueFISP sequence was used at 1.5 and 3.0 T and compared with a segmented IR turboFLASH sequence at 1.5 T, which served as the reference method. Infarct volumes and CNR of infarction and normal myocardium were compared with the reference method. Results The PSIR Single-Shot TrueFISP technique allows for imaging nine slices during a single breathhold without adaptation of the inversion time. The mean value of CNR between infarction and normal myocardium was 5.9 at 1.5 T and 12.2 at 3.0 T (magnitude images). The CNR mean value of the reference method was 8.4. The CNR mean value at 3.0 T was significantly (P = 0.03) higher than the mean value of the reference method. The correlation coefficients of the infarct volumes, determined with the PSIR single-shot TrueFISP technique at 1.5 T and at 3.0 T and compared with the reference method, were r = 0.96 (P = 0.001) and r = 0.99 (P = 0.0001). Conclusion The use of PSIR single-shot TrueFISP at 3.0 T allows for accurate detection and assessment of myocardial infarction. CNR is significantly higher at 3.0 T compared with 1.5 T. The PSIR single-shot technique at 3.0 T provides a higher CNR than the segmented reference technique at 1.5 T.

Background —Microvascular obstruction within an area of myocardial infarction indicates worse functional recovery and a higher risk of postinfarction complications. After prolonged coronary occlusion, contrast-enhanced MRI identifies myocardial infarction as a hyperenhanced region containing a hypoenhanced core. Because the time course of microvascular obstruction after infarction/reperfusion is unknown, we examined whether microvascular obstruction reaches its full extent shortly after reperfusion or shows significant progression over the following 2 days. Methods and Results —Seven dogs underwent 90-minute balloon occlusion of the left anterior descending coronary artery (LAD) followed by reflow. Gadolinium-DTPA–enhanced MRI performed at 2, 6, and 48 hours after reperfusion was compared with radioactive microsphere blood flow (MBF) measurements and myocardial staining to define microvascular obstruction (thioflavin S) and infarct size (triphenyltetrazolium chloride, TTC). The MRI hypoenhanced region increased 3-fold during 48 hours after reperfusion (3.2±1.8%, 6.7±4.4%, and 9.9±3.2% of left ventricular mass at 2, 6, and 48 hours, respectively, P r =0.99 and thioflavin S, r =0.93). MRI hyperenhancement also increased (21.7±4.0%, 24.3±4.6%, and 28.8±5.1% at 2, 6, and 48 hours, P r =0.92). The microvascular obstruction/infarct size ratio increased from 13.0±4.8% to 22.6±8.9% and to 30.4±4.2% over 48 hours ( P =0.024). Conclusions —The extent of microvascular obstruction and the infarct size increase significantly over the first 48 hours after myocardial infarction. These results are consistent with progressive microvascular and myocardial injury well beyond coronary occlusion and reflow.

Background The ability of the myocyte to maintain an ionic concentration gradient is perhaps the best indication of myocardial viability. We studied the relationship of 23 Na MRI intensity to viability and explored the potential of fast-imaging techniques to reduce 23 Na imaging times in rabbits and dogs. Methods and Results Eighteen rabbits underwent in situ coronary artery occlusion and reperfusion. The hearts were then either imaged following isolation and perfusion with cardioplegic solution (n=6), imaged in vivo (n=6), or analyzed for 23 Na content and relaxation times (n=12). Normal rabbits (n=6) and dogs (n=4) were imaged to examine the effect of animal size on 23 Na image quality. 23 Na imaging times were 7, 11, and 4 minutes for isolated rabbits, in vivo rabbits, and in vivo dogs, respectively. Infarcted, reperfused regions, identified by triphenyltetrazolium chloride staining, showed a significant elevation in 23 Na image intensity compared with viable regions (isolated, 42±5%, P P 23 Na MR spectroscopy showed that [Na + ] was higher in nonviable than viable myocardium (isolated, 99±4 versus 61±2 mmol/L; in vivo, 91±2 versus 38±1 mmol/L; P Conclusions Following acute infarction with reperfusion, a regional increase in 23 Na MR image intensity is associated with nonviable myocardium. Fast gradient-echo imaging techniques reduce 23 Na imaging times to a few minutes, suggesting that 23 Na MR imaging has the potential to become a useful experimental and clinical tool.