Myocardial Blood Flow Quantification Using Stress Cardiac Magnetic Resonance Improves Detection of Coronary Artery Disease.

BACKGROUND: Myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) using stress cardiovascular magnetic resonance (CMR) have been shown to identify epicardial coronary artery disease. However, comparative analysis between quantitative perfusion and conventional qualitative assessment (QA) remains limited. OBJECTIVES: The aim of this multicenter study was to test the hypothesis that quantitative stress MBF (sMBF) and MPR analysis can identify obstructive coronary artery disease (obCAD) with comparable performance as QA of stress CMR performed by experienced physicians in interpretation. METHODS: The analysis included 127 individuals (mean age 62 ± 16 years, 84 men [67%]) who underwent stress CMR. obCAD was defined as the presence of stenosis ≥50% in the left main coronary artery or ≥70% in a major vessel. Each patient, coronary territory, and myocardial segment was categorized as having either obCAD or no obCAD (noCAD). Global, per coronary territory, and segmental MBF and MPR values were calculated. QA was performed by 4 CMR experts. RESULTS: At the patient level, global sMBF and MPR were significantly lower in subjects with obCAD than in those with noCAD, with median values of sMBF of 1.5 mL/g/min (Q1-Q3: 1.2-1.8 mL/g/min) vs 2.4 mL/g/min (Q1-Q3: 2.1-2.7 mL/g/min) (P < 0.001) and median values of MPR of 1.3 (Q1-Q3: 1.0-1.6) vs 2.1 (Q1-Q3: 1.6-2.7) (P < 0.001). At the coronary artery level, sMBF and MPR were also significantly lower in vessels with obCAD compared with those with noCAD. Global sMBF and MPR had areas under the curve (AUCs) of 0.90 (95% CI: 0.84-0.96) and 0.86 (95% CI: 0.80-0.93). The AUCs for QA by 4 physicians ranged between 0.69 and 0.88. The AUC for global sMBF and MPR was significantly better than the average AUC for QA. CONCLUSIONS: This study demonstrates that sMBF and MPR using dual-sequence stress CMR can identify obCAD more accurately than qualitative analysis by experienced CMR readers.

Wideband radiofrequency pulse sequence for evaluation of myocardial scar in patients with cardiac implantable devices.

Background: Cardiac magnetic resonance is a useful clinical tool to identify late gadolinium enhancement in heart failure patients with implantable electronic devices. Identification of LGE in patients with CIED is limited by artifact, which can be improved with a wide band radiofrequency pulse sequence. Objective: The authors hypothesize that image quality of LGE images produced using wide-band pulse sequence in patients with devices is comparable to image quality produced using standard LGE sequences in patients without devices. Methods: Two independent readers reviewed LGE images of 16 patients with CIED and 7 patients without intracardiac devices to assess for image quality, device-related artifact, and presence of LGE using the American Society of Echocardiography/American Heart Association 17 segment model of the heart on a 4-point Likert scale. The mean and standard deviation for image quality and artifact rating were determined. Inter-observer reliability was determined by calculating Cohen's kappa coefficient. Statistical significance was determined by T-test as a p {less than or equal to} 0.05 with a 95% confidence interval. Results: All patients underwent CMR without any adverse events. Overall IQ of WB LGE images was significantly better in patients with devices compared to standard LGE in patients without devices (p = 0.001) with reduction in overall artifact rating (p = 0.05). Conclusion: Our study suggests wide-band pulse sequence for LGE can be applied safely to heart failure patients with devices in detection of LV myocardial scar while maintaining image quality, reducing artifact, and following routine imaging protocol after intravenous gadolinium contrast administration.

Comparison of dual-bolus versus dual-sequence techniques for determining myocardial blood flow and myocardial perfusion reserve by cardiac magnetic resonance stress perfusion: From the Automated Quantitative analysis of myocardial perfusion cardiac Magnetic Resonance Consortium.

BACKGROUND: Quantitative stress cardiac magnetic resonance (CMR) can be performed using the dual-sequence (DS) technique or dual-bolus (DB) method. It is unknown if DS and DB produce similar results for myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). The study objective is to investigate if there are any differences between DB- and DS-derived MBF and MPR. METHODS: Retrospective observational study with 168 patients who underwent stress CMR. DB and DS methods were simultaneously performed on each patient on the same day. Global and segmental stress MBF and rest MBF values were collected. RESULTS: Using Bland-Altman analysis, segmental and global stress MBF values were higher in DB than DS (0.22 ± 0.60 mL/g/min, p < 0.001 and 0.20 ± 0.48 mL/g/min, p = 0.005, respectively) with strong correlation (r = 0.81, p < 0.001 for segmental and r = 0.82, p < 0.001 for global). In rest MBF, segmental and global DB values were higher than by DS (0.15 ± 0.51 mL/g/min, p < 0.001 and 0.14 ± 0.36 mL/g/min, p = 0.011, respectively) with strong correlation (r = 0.81, p < 0.001 and r = 0.77, p < 0.001). Mean difference between MPR by DB and DS was -0.02 ± 0.68 mL/g/min (p = 0.758) for segmental values and -0.01 ± 0.49 mL/g/min (p = 0.773) for global values. MPR values correlated strongly as well in both segmental and global, both (r = 0.74, p < 0.001) and (r = 0.75, p < 0.001), respectively. CONCLUSION: There is a very good correlation between DB- and DS-derived MBF and MPR values. However, there are significant differences between DB- and DS-derived global stress and rest MBF. While MPR values did not show statistically significant differences between DB and DS methods.

Clinical utility of a rapid two-dimensional balanced steady-state free precession sequence with deep learning reconstruction.

BACKGROUND: Cardiovascular magnetic resonance (CMR) cine imaging is still limited by long acquisition times. This study evaluated the clinical utility of an accelerated two-dimensional (2D) cine sequence with deep learning reconstruction (Sonic DL) to decrease acquisition time without compromising quantitative volumetry or image quality. METHODS: A sub-study using 16 participants was performed using Sonic DL at two different acceleration factors (8× and 12×). Quantitative left-ventricular volumetry, function, and mass measurements were compared between the two acceleration factors against a standard cine method. Following this sub-study, 108 participants were prospectively recruited and imaged using a standard cine method and the Sonic DL method with the acceleration factor that more closely matched the reference method. Two experienced clinical readers rated images based on their diagnostic utility and performed all image contouring. Quantitative contrast difference and endocardial border sharpness were also assessed. Left- and right-ventricular volumetry, left-ventricular mass, and myocardial strain measurements were compared between cine methods using Bland-Altman plots, Pearson's correlation, and paired t-tests. Comparative analysis of image quality was measured using Wilcoxon-signed-rank tests and visualized using bar graphs. RESULTS: Sonic DL at an acceleration factor of 8 more closely matched the reference cine method. There were no significant differences found across left ventricular volumetry, function, or mass measurements. In contrast, an acceleration factor of 12 resulted in a 6% (5.51/90.16) reduction of measured ejection fraction when compared to the standard cine method and a 4% (4.32/88.98) reduction of measured ejection fraction when compared to Sonic DL at an acceleration factor of 8. Thus, Sonic DL at an acceleration factor of 8 was chosen for downstream analysis. In the larger cohort, this accelerated cine sequence was successfully performed in all participants and significantly reduced the acquisition time of cine images compared to the standard 2D method (reduction of 37% (5.98/16) p < 0.0001). Diagnostic image quality ratings and quantitative image quality evaluations were statistically not different between the two methods (p > 0.05). Left- and right-ventricular volumetry and circumferential and radial strain were also similar between methods (p > 0.05) but left-ventricular mass and longitudinal strain were over-estimated using the proposed accelerated cine method (mass over-estimated by 3.36 g/m2, p < 0.0001; longitudinal strain over-estimated by 1.97%, p = 0.001). CONCLUSION: This study found that an accelerated 2D cine method with DL reconstruction at an acceleration factor of 8 can reduce CMR cine acquisition time by 37% (5.98/16) without significantly affecting volumetry or image quality. Given the increase of scan time efficiency, this undersampled acquisition method using deep learning reconstruction should be considered for routine clinical CMR.

Myocardial Blood Flow Quantified Using Stress Cardiac Magnetic Resonance After Mild COVID-19 Infection.

BACKGROUND: Severe COVID-19 infection is known to alter myocardial perfusion through its effects on the endothelium and microvasculature. However, the majority of patients with COVID-19 infection experience only mild symptoms, and it is unknown if their myocardial perfusion is altered after infection. OBJECTIVES: The authors aimed to determine if there are abnormalities in myocardial blood flow (MBF), as measured by stress cardiac magnetic resonance (CMR), in individuals after a mild COVID-19 infection. METHODS: We conducted a prospective, comparative study of individuals who had a prior mild COVID-19 infection (n = 30) and matched controls (n = 26) using stress CMR. Stress and rest myocardial blood flow (sMBF, rMBF) were quantified using the dual sequence technique. Myocardial perfusion reserve was calculated as sMBF/rMBF. Unpaired t-tests were used to test differences between the groups. RESULTS: The median time interval between COVID-19 infection and CMR was 5.6 (IQR: 4-8) months. No patients with the COVID-19 infection required hospitalization. Symptoms including chest pain, shortness of breath, syncope, and palpitations were more commonly present in the group with prior COVID-19 infection than in the control group (57% vs 7%, P < 0.001). No significant differences in rMBF (1.08 ± 0.27 mL/g/min vs 0.97 ± 0.29 mL/g/min, P = 0.16), sMBF (3.08 ± 0.79 mL/g/min vs 3.06 ± 0.89 mL/g/min, P = 0.91), or myocardial perfusion reserve (2.95 ± 0.90 vs 3.39 ± 1.25, P = 0.13) were observed between the groups. CONCLUSIONS: This study suggests that there are no significant abnormalities in rest or stress myocardial perfusion, and thus microvascular function, in individuals after mild COVID-19 infection.

Reliability of respiratory-gated real-time two-dimensional cine incorporating deep learning reconstruction for the assessment of ventricular function in an adult population.

This study aimed to assess the image quality and accuracy of respiratory-gated real-time two-dimensional (2D) cine incorporating deep learning reconstruction (DLR) for the quantification of biventricular volumes and function compared with those of the standard reference, that is, breath-hold 2D balanced steady-state free precession (bSSFP) cine, in an adult population. Twenty-four patients (15 men, mean age 50.7 ± 16.5 years) underwent cardiac magnetic resonance for clinical indications, and 2D DLR and bSSFP cine were acquired on the short-axis view. The image quality scores were based on three main criteria: blood-to-myocardial contrast, endocardial edge delineation, and presence of motion artifacts throughout the cardiac cycle. Biventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and left ventricular mass (LVM) were analyzed. The 2D DLR cine had significantly shorter scan time than bSSFP (41.0 ± 11.3 s vs. 327.6 ± 65.8 s; p < 0.0001). Despite an analysis of endocardial edge definition and motion artifacts showed significant impairment using DLR cine compared with bSSFP (p < 0.01), the two sequences demonstrated no significant difference in terms of biventricular EDV, ESV, SV, and EF (p > 0.05). Moreover, the linear regression yielded good agreement between the two techniques (r ≥ 0.76). However, the LVM was underestimated for DLR cine (109.8 ± 34.6 g) compared with that for bSSFP (116.2 ± 40.2 g; p = 0.0291). Respiratory-gated 2D DLR cine is a reliable technique that could be used in the evaluation of biventricular volumes and function in an adult population.

Improving the robustness of MOLLI T1 maps with a dedicated motion correction algorithm.

Myocardial tissue T1 constitutes a reliable indicator of several heart diseases related to extracellular changes (e.g. edema, fibrosis) as well as fat, iron and amyloid content. Magnetic resonance (MR) T1-mapping is typically achieved by pixel-wise exponential fitting of a series of inversion or saturation recovery measurements. Good anatomical alignment between these measurements is essential for accurate T1 estimation. Motion correction is recommended to improve alignment. However, in the case of inversion recovery sequences, this correction is compromised by the intrinsic contrast variation between frames. A model-based, non-rigid motion correction method for MOLLI series was implemented and validated on a large database of cardiac clinical cases (n = 186). The method relies on a dedicated similarity metric that accounts for the intensity changes caused by T1 magnetization relaxation. The results were compared to uncorrected series and to the standard motion correction included in the scanner. To automate the quantitative analysis of results, a custom data alignment metric was defined. Qualitative evaluation was performed on a subset of cases to confirm the validity of the new metric. Motion correction caused noticeable (i.e. > 5%) performance degradation in 12% of cases with the standard method, compared to 0.3% with the new dedicated method. The average alignment quality was 85% ± 9% with the default correction and 90% ± 7% with the new method. The results of the qualitative evaluation were found to correlate with the quantitative metric. In conclusion, a dedicated motion correction method for T1 mapping MOLLI series has been evaluated on a large database of clinical cardiac MR cases, confirming its increased robustness with respect to the standard method implemented in the scanner.

Feasibility of late gadolinium enhancement (LGE) in ischemic cardiomyopathy using 2D-multisegment LGE combined with artificial intelligence reconstruction deep learning noise reduction algorithm.

BACKGROUND: Despite the low spatial resolution of 2D-multisegment late gadolinium enhancement (2D-MSLGE) sequences, it may be useful in uncooperative patients instead of standard 2D single segmented inversion recovery gradient echo late gadolinium enhancement sequences (2D-SSLGE). The aim of the study is to assess the feasibility and comparison of 2D-MSLGE reconstructed with artificial intelligence reconstruction deep learning noise reduction (NR) algorithm compared to standard 2D-SSLGE in consecutive patients with ischemic cardiomyopathy (ICM). METHODS: Fifty-seven patients with known ICM referred for a clinically indicated CMR were enrolled in this study. 2D-MSLGE were reconstructed using a growing level of NR (0%,25%,50%,75%and 100%). Subjective image quality, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were evaluated in each dataset and compared to standard 2D-SSLGE. Moreover, diagnostic accuracy, LGE mass and scan time were compared between 2D-MSLGE with NR and 2D-SSLGE. RESULTS: The application of NR reconstruction ≥50% to 2D-MSLGE provided better subjective image quality, CNR and SNR compared to 2D-SSLGE (p < 0.01). The best compromise in terms of subjective and objective image quality was observed for values of 2D-MSLGE 75%, while no differences were found in terms of LGE quantification between 2D-MSLGE versus 2D-SSLGE, regardless the NR applied. The sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 2D-MSLGE NR 75% were 87.77%,96.27%,96.13%,88.16% and 94.22%, respectively. Time of acquisition of 2D-MSLGE was significantly shorter compared to 2D-SSLGE (p < 0.01). CONCLUSION: When compared to standard 2D-SSLGE, the application of NR reconstruction to 2D-MSLGE provides superior image quality with similar diagnostic accuracy.

Influence of motion correction on the visual analysis of cardiac magnetic resonance stress perfusion imaging.

OBJECTIVE: Image post-processing corrects for cardiac and respiratory motion (MoCo) during cardiovascular magnetic resonance (CMR) stress perfusion. The study analyzed its influence on visual image evaluation. MATERIALS AND METHODS: Sixty-two patients with (suspected) coronary artery disease underwent a standard CMR stress perfusion exam during free-breathing. Image post-processing was performed without (non-MoCo) and with MoCo (image intensity normalization; motion extraction with iterative non-rigid registration; motion warping with the combined displacement field). Images were evaluated regarding the perfusion pattern (perfusion deficit, dark rim artifact, uncertain signal loss, and normal perfusion), the general image quality (non-diagnostic, imperfect, good, and excellent), and the reader's subjective confidence to assess the images (not confident, confident, very confident). RESULTS: Fifty-three (non-MoCo) and 52 (MoCo) myocardial segments were rated as 'perfusion deficit', 113 vs. 109 as 'dark rim artifacts', 9 vs. 7 as 'uncertain signal loss', and 817 vs. 824 as 'normal'. Agreement between non-MoCo and MoCo was high with no diagnostic difference per-patient. The image quality of MoCo was rated more often as 'good' or 'excellent' (92 vs. 63%), and the diagnostic confidence more often as "very confident" (71 vs. 45%) compared to non-MoCo. CONCLUSIONS: The comparison of perfusion images acquired during free-breathing and post-processed with and without motion correction demonstrated that both methods led to a consistent evaluation of the perfusion pattern, while the image quality and the reader's subjective confidence to assess the images were rated more favorably for MoCo.

Reliability of respiratory-triggered two-dimensional cine k-adaptive-t-autocalibrating reconstruction for Cartesian sampling for the assessment of biventricular volume and function in patients with repaired tetralogy of Fallot.

OBJECTIVE: To compare left ventricular (LV) and right ventricular (RV) volume, function, and image quality of a respiratory-triggered two-dimensional (2D)-cine k-adaptive-t-autocalibrating reconstruction for Cartesian sampling (2D kat-ARC) with those of the standard reference, namely, breath-hold 2D balanced steady-state free precession (2D SSFP), in patients with repaired tetralogy of Fallot (TOF). METHODS: 30 patients (14 males, mean age 32.2 ± 13.9 years) underwent cardiac magnetic resonance, and 2D kat-ARC and 2D SSFP images were acquired on short-axis view. Biventricular end-diastolic volume (EDV) and end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and LV mass (LVM) were analysed. RESULTS: The 2D kat-ARC had significantly shorter scan time (35.2 ± 9.1 s vs 80.4 ± 16.7 s; p < 0.0001). Despite an analysis of image quality showed significant impairment using 2D kat-ARC compared to 2D SSFP cine (p < 0.0001), the two sequences demonstrated no significant difference in terms of biventricular EDV, LVESV, LVSV, LVEF, and LVM. However, the RVESV was overestimated for 2D kat-ARC compared with that for 2D SSFP (73.8 ± 43.2 ml vs 70.3 ± 44.5 ml, p = 0.0002) and the RVSV and RVEF were underestimated (RVSV = 46.2±20.5 ml vs 49.4 ± 20.4 ml, p = 0.0024; RVEF = 40.2±12.7% vs. 43.5±14.0%, p = 0.0002). CONCLUSION: Respiratory-triggered 2D kat-ARC cine is a reliable technique that could be used in the evaluation of LV volumes and function. ADVANCES IN KNOWLEDGE: 2D cine kat-ARC is a reliable technique for the assessment LV volume and function in patients with repaired TOF.

Improvement of late gadolinium enhancement image quality using a deep learning-based reconstruction algorithm and its influence on myocardial scar quantification.

OBJECTIVES: The aim of this study was to assess the effect of a deep learning (DL)-based reconstruction algorithm on late gadolinium enhancement (LGE) image quality and to evaluate its influence on scar quantification. METHODS: Sixty patients (46 ± 17 years, 50% male) with suspected or known cardiomyopathy underwent CMR. Short-axis LGE images were reconstructed using the conventional reconstruction and a DL network (DLRecon) with tunable noise reduction (NR) levels from 0 to 100%. Image quality of standard LGE images and DLRecon images with 75% NR was scored using a 5-point scale (poor to excellent). In 30 patients with LGE, scar size was quantified using thresholding techniques with different standard deviations (SD) above remote myocardium, and using full width at half maximum (FWHM) technique in images with varying NR levels. RESULTS: DLRecon images were of higher quality than standard LGE images (subjective quality score 3.3 ± 0.5 vs. 3.6 ± 0.7, p < 0.001). Scar size increased with increasing NR levels using the SD methods. With 100% NR level, scar size increased 36%, 87%, and 138% using 2SD, 4SD, and 6SD quantification method, respectively, compared to standard LGE images (all p values < 0.001). However, with the FWHM method, no differences in scar size were found (p = 0.06). CONCLUSIONS: LGE image quality improved significantly using a DL-based reconstruction algorithm. However, this algorithm has an important impact on scar quantification depending on which quantification technique is used. The FWHM method is preferred because of its independency of NR. Clinicians should be aware of this impact on scar quantification, as DL-based reconstruction algorithms are being used. KEY POINTS: • The image quality based on (subjective) visual assessment and image sharpness of late gadolinium enhancement images improved significantly using a deep learning-based reconstruction algorithm that aims to reconstruct high signal-to-noise images using a denoising technique. • Special care should be taken when scar size is quantified using thresholding techniques with different standard deviations above remote myocardium because of the large impact of these advanced image enhancement algorithms. • The full width at half maximum method is recommended to quantify scar size when deep learning algorithms based on noise reduction are used, as this method is the least sensitive to the level of noise and showed the best agreement with visual late gadolinium enhancement assessment.

Image Quality and Reliability of a Novel Dark-Blood Late Gadolinium Enhancement Sequence in Ischemic Cardiomyopathy.

PURPOSE: The aim of this study was to assess the reliability of a 2D dark-blood phase-sensitive late gadolinium enhancement sequence (2D-DBPSLGE) compared with 2D phase-sensitive inversion recovery late gadolinium enhancement sequence (2D-BBPSLGE) in patients with ischemic cardiomyopathy (ICM). MATERIALS AND METHODS: A total of 73 patients with a clinical history of ICM were prospectively enrolled. The following endpoints were evaluated: (a) comparison of image quality between 2D-BBPSLGE and 2D-DBPSLGE for differentiation between blood pool-late gadolinium enhancement (LGE), remote myocardium-LGE, and blood pool-remote myocardium; (b) diagnostic accuracy of 2D-DBPSLGE compared with gold standard 2D-BBPSLGE for the evaluation of infarcted segments; (c) diagnostic accuracy of 2D-DBPSLGE for the evaluation of microvascular obstruction (MVO); (d) comparison of transmurality index between 2D-BBPSLGE and 2D-DBPSLGE; (e) comparison of papillary muscle hyperenhancement between 2D-BBPSLGE and 2D-DBPSLGE; inter-reader agreement for depiction of hyperenhanced segments in both LGE sequences. Data were analyzed using paired t test, Wilcoxon test, and McNemar test, and η coefficient and intercorrelation coefficient (ICC). RESULTS: Image quality was superior for 2D-DBPSLGE for differentiation of blood pool-LGE (P<0.001). 2D-DBPSLGE, compared with 2D-BBPSLGE, showed a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 96.93%, 99.89%, 99.71%, 98.78, and 99.04%, respectively. Concerning MVO detection, 2D-DBPSLGE showed a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 66.67%, 100.00%, 100.00%, 80.95%, and 86.21%, respectively. 2D-DBPSLGE underestimated the transmurality (P=0.007) and identified papillary muscle hyperenhancement (P<0.001). Both LGE sequences showed comparable interobserver agreement for the evaluation of infarcted areas (2D-BBPSLGE: ICC 0.99;2D-DBPSLGE: ICC 0.99). CONCLUSIONS: Compared with 2D-BBPSLGE, 2D-DBPSLGE sequences provide better differentiation between LGE and blood-pool, while underestimating LGE trasmurality and the presence of MVO.

Multiparametric human hepatocellular carcinoma characterization and therapy response evaluation by hyperpolarized (13) C MRSI.

Individual tumor characterization and treatment response monitoring based on current medical imaging methods remain challenging. This work investigates hyperpolarized (13) C compounds in an orthotopic rat hepatocellular carcinoma (HCC) model system before and after transcatheter arterial embolization (TAE). HCC ranks amongst the top six most common cancer types in humans and accounts for one-third of cancer-related deaths worldwide. Early therapy response monitoring could aid in the development of personalized therapy approaches and novel therapeutic concepts. Measurements with selectively (13) C-labeled and hyperpolarized urea, pyruvate and fumarate were performed in tumor-bearing rats before and after TAE. Two-dimensional, slice-selective MRSI was used to obtain spatially resolved maps of tumor perfusion, cell energy metabolic conversion rates and necrosis, which were additionally correlated with immunohistochemistry. All three injected compounds, taken together with their respective metabolites, exhibited similar signal distributions. TAE induced a decrease in blood flow into the tumor and thus a decrease in tumor to muscle and tumor to liver ratios of urea, pyruvate and its metabolites, alanine and lactate, whereas conversion rates remained stable or increased on TAE in tumor, muscle and liver tissue. Conversion from fumarate to malate successfully indicated individual levels of necrosis, and global malate signals after TAE suggested the washout of fumarase or malate itself on necrosis. This study presents a combination of three (13) C compounds as novel candidate biomarkers for a comprehensive characterization of genetically and molecularly diverse HCC using hyperpolarized MRSI, enabling the simultaneous detection of differences in tumor perfusion, metabolism and necrosis. If, as in this study, bolus dynamics are not required and qualitative perfusion information is sufficient, the desired information could be extracted from hyperpolarized fumarate and pyruvate alone, acquired at higher fields with better spectral separation. Copyright © 2016 John Wiley & Sons, Ltd.

Parameterization of hyperpolarized (13)C-bicarbonate-dissolution dynamic nuclear polarization.

OBJECTIVE: (13)C metabolic MRI using hyperpolarized (13)C-bicarbonate enables preclinical detection of pH. To improve signal-to-noise ratio, experimental procedures were refined, and the influence of pH, buffer capacity, temperature, and field strength were investigated. MATERIALS AND METHODS: Bicarbonate preparation was investigated. Bicarbonate was prepared and applied in spectroscopy at 1, 3, 14 T using pure dissolution, culture medium, and MCF-7 cell spheroids. Healthy rats were imaged by spectral-spatial spiral acquisition for spatial and temporal bicarbonate distribution, pH mapping, and signal decay analysis. RESULTS: An optimized preparation technique for maximum solubility of 6 mol/L and polarization levels of 19-21% is presented; T1 and SNR dependency on field strength, buffer capacity, and pH was investigated. pH mapping in vivo is demonstrated. CONCLUSION: An optimized bicarbonate preparation and experimental procedure provided improved T1 and SNR values, allowing in vitro and in vivo applications.

Effects of inner volume field-of-view reduction on myocardial T2 mapping.

BACKGROUND: Inner volume (IV) excitation was explored with respect to scan time reduction of cardiac gated double inversion recovery multi-echo fast spin echo (MEFSE) to measure the transverse relaxation time (T2 ) in the myocardium. METHODS: The IV imaging was achieved by applying orthogonal slice selection for the excitation and refocusing pulses. The T2 map accuracy was investigated using different excitation and refocusing pulses. The performance of IV-MEFSE was compared with MEFSE on phantoms and eight healthy volunteers, acquiring eight echo times in a single breath-hold. RESULTS: Compared with MEFSE, IV-MEFSE allowed a scan time reduction from 26 s to 16 s, but caused a T2 overestimation of approximately 10% due to stimulated echoes. CONCLUSION: IV successfully reduced the scan time to a single breath-hold feasible for many patients and remarkably facilitated the scan prescription, because there was no image aliasing concern. Care should be taken in using IV for T2 mapping because of T2 relaxation time overestimation.

Quantified pH imaging with hyperpolarized (13) C-bicarbonate.

PURPOSE: Because pH plays a crucial role in several diseases, it is desirable to measure pH in vivo noninvasively and in a spatially localized manner. Spatial maps of pH were quantified in vitro, with a focus on method-based errors, and applied in vivo. METHODS: In vitro and in vivo (13) C mapping were performed for various flip angles for bicarbonate (BiC) and CO2 with spectral-spatial excitation and spiral readout in healthy Lewis rats in five slices. Acute subcutaneous sterile inflammation was induced with Concanavalin A in the right leg of Buffalo rats. pH and proton images were measured 2 h after induction. RESULTS: After optimizing the signal to noise ratio of the hyperpolarized (13) C-bicarbonate, error estimation of the spectral-spatial excited spectrum reveals that the method covers the biologically relevant pH range of 6 to 8 with low pH error (< 0.2). Quantification of pH maps shows negligible impact of the residual bicarbonate signal. pH maps reflect the induction of acute metabolic alkalosis. Inflamed, infected regions exhibit lower pH. CONCLUSION: Hyperpolarized (13) C-bicarbonate pH mapping was shown to be sensitive in the biologically relevant pH range. The mapping of pH was applied to healthy in vivo organs and interpreted within inflammation and acute metabolic alkalosis models.

Multisite Kinetic Modeling of (13)C Metabolic MR Using [1-(13)C]Pyruvate.

Hyperpolarized (13)C imaging allows real-time in vivo measurements of metabolite levels. Quantification of metabolite conversion between [1-(13)C]pyruvate and downstream metabolites [1-(13)C]alanine, [1-(13)C]lactate, and [(13)C]bicarbonate can be achieved through kinetic modeling. Since pyruvate interacts dynamically and simultaneously with its downstream metabolites, the purpose of this work is the determination of parameter values through a multisite, dynamic model involving possible biochemical pathways present in MR spectroscopy. Kinetic modeling parameters were determined by fitting the multisite model to time-domain dynamic metabolite data. The results for different pyruvate doses were compared with those of different two-site models to evaluate the hypothesis that for identical data the uncertainty of a model and the signal-to-noise ratio determine the sensitivity in detecting small physiological differences in the target metabolism. In comparison to the two-site exchange models, the multisite model yielded metabolic conversion rates with smaller bias and smaller standard deviation, as demonstrated in simulations with different signal-to-noise ratio. Pyruvate dose effects observed previously were confirmed and quantified through metabolic conversion rate values. Parameter interdependency allowed an accurate quantification and can therefore be useful for monitoring metabolic activity in different tissues.

Bolus tracking for improved metabolic imaging of hyperpolarised compounds.

Dynamic nuclear polarisation has enabled real-time metabolic imaging of pyruvate and its metabolites. Conventional imaging sequences rely on predefined settings and do not account for intersubject variations in biological parameters such as perfusion. We present a fully automatic real-time bolus tracking sequence for hyperpolarised substrates which starts the imaging acquisition at a defined point on the bolus curve. This reduces artefacts due to signal change and allows for a more efficient use of hyperpolarised magnetisation. For single time point imaging methods, bolus tracking enables a more reliable and consistent quantification of metabolic activity. An RF excitation with a small flip angle is used to obtain slice-selective pyruvate tracking information in rats. Moreover, in combination with a copolarised urea and pyruvate injection, spectrally selective tracking on urea allows obtaining localised bolus tracking information without depleting the pyruvate signal. Particularly with regard to clinical application, the bolus tracking technique could provide an important step towards a routine assessment protocol which removes operator dependencies and ensures comparable results.

In vivo measurement of apparent diffusion coefficients of hyperpolarized ¹³C-labeled metabolites.

The combination of hyperpolarized MRS with diffusion weighting (dw) allows for determination of the apparent diffusion coefficient (ADC), which is indicative of the intra- or extracellular localization of the metabolite. Here, a slice-selective pulsed-gradient spin echo sequence was implemented to acquire a series of dw spectra from rat muscle in vivo to determine the ADCs of multiple metabolites after a single injection of hyperpolarized [1- ¹³C]pyruvate. An optimal control optimized universal-rotation pulse was used for refocusing to minimize signal loss caused by B1 imperfections. Non-dw spectra were acquired interleaved with the dw spectra and these were used to correct for signal decay during the acquisition as a result of T1 decay, pulse imperfections, flow etc. The data showed that the ADC values for [1- ¹³C]lactate (0.4-0.7 µm² /ms) and [1- ¹³C]alanine (0.4-0.9 µm² /ms) were about a factor of two lower than the ADC of [1- ¹³C]pyruvate (1.1-1.5 µm²/ms). This indicates a more restricted diffusion space for the former two metabolites consistent with lactate and alanine being intracellular. The higher ADC for pyruvate (similar to the proton ADC) reflected that the injected substance was not confined inside the muscle cells but also present extracellular.

Multimodal assessment of in vivo metabolism with hyperpolarized [1-13C]MR spectroscopy and 18F-FDG PET imaging in hepatocellular carcinoma tumor-bearing rats.

UNLABELLED: Abnormalities of tumor metabolism can be exploited for molecular imaging. PET imaging of (18)F-FDG is a well-established method using the avid glucose uptake of tumor cells. (13)C MR spectroscopic imaging (MRSI) of hyperpolarized [1-(13)C]pyruvate and its metabolites, meanwhile, represents a new method to study energy metabolism by visualizing, for example, the augmented lactate dehydrogenase activity in tumor cells. Because of rapid signal loss, this method underlies strict temporal limitations, and the acquisition of data-encoding spatial, temporal, and spectral information within this time frame-is challenging. The object of our study was to compare spectroscopic images with (18)F-FDG PET images for visualizing tumor metabolism in a rat model. METHODS: (13)C MRSI with IDEAL (Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation) chemical shift imaging in combination with single-shot spiral acquisition was used to obtain dynamic data from 23 rats bearing a subcutaneous hepatocellular carcinoma and from reference regions of the same animals. Static and dynamic analysis of (18)F-FDG PET images of the same animals was performed. The data were analyzed qualitatively (visual assessment) and quantitatively (magnitude and dynamics of (18)F-FDG uptake, (13)C MRSI dynamics, and physiologic parameters). RESULTS: In most animals increased [1-(13)C]lactate signals in the tumor could be detected by simple display of integrated [1-(13)C]lactate images with corresponding enhanced (18)F-FDG uptake. Low [1-(13)C]pyruvate or [1-(13)C]lactate signals did not correlate with histologic or physiologic parameters. Significantly less pyruvate reached the tumors than the gastrointestinal tract, but in tumors a significantly higher amount of pyruvate was converted to lactate and alanine within seconds after intravenous administration. CONCLUSION: This study reveals that PET and (13)C MRSI can be used to visualize increased glycolytic flux in malignant tissue. The combination of signals will allow the quantitative dissection of substrate metabolism, with respect to uptake and downstream metabolic pathways. Although hyperpolarized [1-(13)C]pyruvate increases the sensitivity of MR imaging, signal-to-noise ratio constraints still apply for spatially and temporally resolved (13)C MRSI, emphasizing the need for further MR methodologic development. These first imaging data suggest the feasibility of (13)C MRSI for future clinical use.