DCE-MRI to distinguish all monoclonal plasma cell disease stages and correlation with diffusion-weighted MRI/PET-based biomarkers in a hybrid simultaneous whole body-2-[18F]FDG-PET/MRI imaging approach.

BACKGROUND: Dynamic contrast-enhanced-MRI (DCE-MRI) is able to study bone marrow angiogenesis in patients with multiple myeloma (MM) and asymptomatic precursor diseases but its role in the management of MM has not yet been established. The aims of this prospective study was to compare DCE-MRI-based parameters between all monoclonal plasma cell disease stages in order to find out discriminatory parameters and to seek correlations with other diffusion-weighted MRI and positron emission tomography (PET)-based biomarkers in a hybrid simultaneous whole-body-2-[18F]fluorodeoxyglucose (FDG)-PET/MRI (WB-2-[18F]FDG-PET/MRI) imaging approach. METHODS: Patients with newly diagnosed Monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) or symptomatic MM according to international myeloma working group and underwent WB-2-[18F]FDG-PET/MRI imaging including bone marrow DCE sequences at the Nantes University Hospital were prospectively enrolled in this study before receiving treatment. RESULTS: One hundred and sixty-seven patients (N = 167, mean age: 64 years ± 11 [Standard deviation], 66 males) were considered for the analysis. DCE-MRI-based Peak Enhancement Intensity (PEI), Time to PEI (TPEI) and their maximum intensity time ratio (MITR: PEI/TPEI) values were significantly different between the different monoclonal plasma cell disease stages, PEI values increasing and TPEI values decreasing progressively along the spectrum of plasma cell disorders, from MGUS stage to symptomatic multiple myeloma. PEI values were significantly higher in patients with diffuse bone marrow involvement (either in PET or in MRI images) than in those without diffuse bone marrow involvement, unlike TPEI values. PEI and TPEI values were not significantly different between patients with or without focal bone lesions. CONCLUSION: Different DCE-MRI-based parameters (PEI, TPEI, MITR) could significantly differentiate all monoclonal plasma cell disease stages and complemented conventional MRI and PET-based biomarkers.

Hybrid simultaneous whole-body 2-[18F]FDG-PET/MRI imaging in newly diagnosed multiple myeloma: first diagnostic performance and clinical added value results.

OBJECTIVES: Mixing diagnostic and prognostic data provided by whole-body MRI (WB-MRI) and 2-18F-fluorodeoxyglucose (2-[18F]FDG) positron emission tomography (2-[18F]FDG-PET) from a single simultaneous imaging technique for newly diagnosed multiple myeloma (NDMM) initial workup seems attractive. However, to date, the published data are scarce and this possibility has not been fully explored. In this prospective study, we aimed to explore the diagnostic performance and added clinical value of WB-2-[18F]FDG-PET/MRI imaging in NDMM. METHODS: All patients with confirmed NDMM at the Nantes University Hospital were prospectively enrolled in this study and underwent WB-2-[18F]FDG-PET/MRI imaging on a 3-T Biograph mMR before receiving treatment. Before imaging, they were considered either as symptomatic or as smoldering MM (SMM). Diagnostic performance of global WB-2-[18F]FDG-PET/MRI imaging, as well as PET and MRI separately for FL and diffuse BMI detection, was assessed and compared in each group. PET-based (maximal standardized uptake value, SUVmax) and MRI-based (mean apparent diffusion coefficient value, ADCmean) quantitative features were collected for FL/para-medullary disease (PMD)/bone marrow and were compared. RESULTS: A total of 52 patients were included in this study. PET and MRI were equally effective at detecting patients with FL (69% vs. 75%) and with diffuse BMI (62% for both) in the symptomatic MM group. WB-2-[18F]FDG-PET/MRI imaging detected FL in 22% of patients with SMM (with a higher diagnostic performance for MRI), resulting in a significant impact on clinical management in this population. SUVmax and ADCmean quantitative features were weakly or not correlated. CONCLUSIONS: WB-2-[18F]FDG-PET/MRI could represent the next-generation imaging modality for MM. KEY POINTS: • Whole-body 2-[18F]FDG-PET/MRI imaging detected at least one focal bone lesion in 75% of patients with symptomatic multiple myeloma, and PET and MRI were equally effective at identifying patients with a focal bone lesion. • Whole-body 2-[18F]FDG-PET/MRI imaging detected a focal bone lesion in 22% of patients with smoldering multiple myeloma (with a higher diagnostic performance for MRI). • MRI had a significant impact on clinical management of smoldering multiple myeloma.

Chest PET/MRI in Solid Cancers: Comparing the Diagnostic Performance of a Free-Breathing 3D-T1-GRE Stack-of-Stars Volume Interpolated Breath-Hold Examination (StarVIBE) Acquisition With That of a 3D-T1-GRE Volume Interpolated Breath-Hold Examination (VIBE) for Chest Staging During Whole-Body PET/MRI.

BACKGROUND: Whole-body positron emission tomography/magnetic resonance imaging (WB-PET/MRI) is increasingly used in oncology. However, chest staging remains challenging. PURPOSE: To compare the diagnostic performance of a free-breathing 3D-T1-GRE stack-of-stars volume interpolated breath-hold examination (StarVIBE) with that of a 3D-T1-GRE volume interpolated breath-hold examination (VIBE) during WB-PET/MRI for chest staging. STUDY TYPE: Retrospective, cohort study. POPULATION: One hundred and twenty-three patients were referred for initial staging of solid cancer, 46 of whom had pulmonary nodules and 14 had pulmonary metastasis. FIELD STRENGTH/SEQUENCE: Free-breathing 3D-T1-GRE stack-of-stars (StarVIBE) and Cartesian 3D-T1-GRE VIBE at 3.0 T. ASSESSMENT: Image quality was assessed using a 4-point scale and using the signal-to-noise ratio (SNR) of lung parenchyma and contrast-to-noise ratio (CNR) of pulmonary nodules. Diagnostic performances of both sequences were determined by three independent radiologists for detection of pulmonary nodules, lymph node involvement, and bone metastases using chest CT, pathology, and follow-up as reference standards. STATISTICAL TESTS: Paired Student's t-test; chi-squared; Fisher's exact test. A P value <0.05 was considered statistically significant. RESULTS: StarVIBE quality was judged as better in 34% of cases and at least equivalent to VIBE in 89% of cases, with significantly higher quality scores (4 [4-4] vs. 3 [3-4], respectively). SNR and CNR values were significantly higher with StarVIBE (8 ± 1.3 and 9.7 ± 4.6, respectively) than with VIBE (1.8 ± 0.2 and 5.5 ± 3.3, respectively). Compared to VIBE, StarVIBE showed significantly higher sensitivity (73% [95% CI 62-82] vs. 44% [95% CI 33-55], respectively) and specificity (95% [95% CI 88-99] vs. 67% [95% CI 56-77]) for pulmonary nodules detection and significantly higher sensitivity (100% [95% CI 89-100] vs. 67% [95% CI 48-82], respectively) for detection of lymph node involvement. Sensitivities for bone metastases detection were not significantly different (100% [95% CI 88-100] vs. 82% [95% CI 63-94], P = 0.054). DATA CONCLUSION: Owing to improved SNR and CNR and spatial resolution, a free-breathing 3D stack-of-stars T1-GRE sequence improves chest staging in comparison with standard 3D-T1-GRE VIBE and may be integrated in WB-PET/MRI acquisitions for initial staging of solid cancer. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Impact of the 18F-FDG-PET/MRI on Metastatic Staging in Patients with Hepatocellular Carcinoma: Initial Results from 104 Patients.

Optimal HCC therapeutic management relies on accurate tumor staging. Our aim was to assess the impact of 18F-FDG-WB-PET/MRI on HCC metastatic staging, compared with the standard of care CT-CAP/liver MRI combination, in patients with HCC referred on a curative intent or before transarterial radioembolization. One hundred and four consecutive patients followed for HCC were retrospectively included. The WB-PET/MRI was compared with the standard of care CT-CAP/liver MRI combination for HCC metastatic staging, with pathology, followup, and multidisciplinary board assessment as a reference standard. Thirty metastases were identified within 14 metastatic sites in 11 patients. The sensitivity of WB-PET/MRI for metastatic sites and metastatic patients was significantly higher than that of the CT-CAP/liver MRI combination (respectively 100% vs. 43%, p = 0.002; and 100% vs. 45%, p = 0.01). Metastatic sites missed by CT-CAP were bone (n = 5) and distant lymph node (n = 3) in BCLC C patients. For the remaining 93 nonmetastatic patients, three BCLC A patients identified as potentially metastatic on the CT-CAP/liver MRI combination were correctly ruled out with the WB-PET/MRI without significant increase in specificity (100% vs. 97%; p = 0.25). The WB-PET/MRI may improve HCC metastatic staging and could be performed as a "one-stop-shop" examination for HCC staging with a significant impact on therapeutic management in about 10% of patients especially in locally advanced HCC.

18F-sodium fluoride PET/MRI myocardial imaging in patients with suspected cardiac amyloidosis.

BACKGROUND: We evaluated the diagnostic performance of 18F-NaF PET/MRI in patients with suspected cardiac amyloidosis (CA). METHODS: Twenty-seven consecutive patients underwent myocardial PET 1 hour after injection of 4 MBq/kg 18F-NaF with simultaneous MRI including cine-MRI, T1 and T2 mapping, first-pass and late gadolinium enhancement (LGE). 18F-NaF uptake was measured visually and semi-quantitatively by calculating myocardium-to-blood pool (M/B) ratios. CA was confirmed histologically. RESULTS: Transthyretin (TTR)-CA was diagnosed in 16 patients, light-chain (AL)-CA in 7, and no-CA in 4. Visual interpretation of 18F-NaF images revealed a relative increase in myocardial uptake in only 3 patients, all with TTR CA, and a relative decrease in 13, including 7 AL CA, 3 no-CA, and 3 TTR CA. M/B ratios were significantly higher in TTR CA (1.00 ± 0.12) than in AL CA (0.81 ± 0.06, P = 0.001) or in no-CA (0.73 ± 0.16, P = 0.006). The optimal M/B cut-off to distinguish TTR CA from AL CA was ≥ 0.90 (Fischer, P = 0.0005). By comparison, classification of patients using 99mTc-HMDP heart-to-mediastinum ratios with the previously published cut-off ≥ 1.21 reached higher significance (P < 0.0001). Among MRI parameters, myocardial T1, LGE score, and extracellular volume were higher in CA than in no-CA patients, 1409 ± 76 vs 1278 ± 35 ms (P = 0.004), 10.35 ± 5.30 vs 3.50 ± 3.42 (P = 0.03), and 46 ± 10 vs 33 ± 8 % (P = 0.01), respectively. CONCLUSION: 18F-NaF PET/MRI shows good diagnostic performance when semi-quantification is used. However, contrast is low and visual interpretation may be challenging in routine. PET/MRI could constitute a one-stop-shop evaluation of amyloid load and cardiac function in patients needing rapid work-up.

Compressed sensing real-time cine imaging for assessment of ventricular function, volumes and mass in clinical practice.

OBJECTIVES: This study was conducted in order to evaluate the accuracy of a compressed sensing (CS) real-time single-breath-hold cine sequence for the assessment of left and right ventricular functional parameters in daily practice. METHODS: Cardiac magnetic resonance (CMR) cine images were acquired from 100 consecutive patients using both the reference segmented multi-breath-hold steady-state free precession (SSFP) acquisition and a prototype single-breath-hold real-time CS sequence, providing the same slice number, position, and thickness. For both sequences, the left (LV) and right ventricular (RV) ejection fractions (EF) and end-diastolic volumes (EDV) were assessed as well as LV mass (LVM). The visualization of wall-motion disorders (WMD) and signal void related to mitral or tricuspid regurgitation was also analyzed. RESULTS: The CS sequence mean scan time was 23 ± 6 versus 510 ± 109 s for the multi-breath-hold SSFP sequence (p < 0.001). There was an excellent correlation between the two sequences regarding mean LVEF (r = 0.995), LVEDV (r = 0.997), LVM (r = 0.981), RVEF (r = 0.979), and RVEDV (r = 0.983). Moreover, inter- and intraobserver agreements were very strong with intraclass correlations of 0.96 and 0.99, respectively. On CS images, mitral or tricuspid regurgitation visualization was good (AUC = 0.85 and 0.81, respectively; ROC curve analysis) and wall-motion disorder visualization was excellent (AUC ≥ 0.97). CONCLUSION: CS real-time single-breath-hold cine imaging reduces CMR scan duration by almost 20 times in daily practice while providing reliable measurements of both left and right ventricles. There was no clinically relevant information loss regarding valve regurgitation and wall-motion disorder depiction. KEY POINTS: • Compressed sensing single-breath-hold real-time cine imaging is a reliable sequence in daily practice. • Fast CS real-time imaging reduces CMR scan time and improves patient workflow. • There is no clinically relevant information loss with CS regarding heart valve regurgitation or wall-motion disorders.

Validation of the Strain Assessment of a Phantom of Abdominal Aortic Aneurysm: Comparison of Results Obtained From Magnetic Resonance Imaging and Stereovision Measurements.

Predicting aortic aneurysm ruptures is a complex problem that has been investigated by many research teams over several decades. Work on this issue is notably complex and involves both the mechanical behavior of the artery and the blood flow. Magnetic resonance imaging (MRI) can provide measurements concerning the shape of an organ and the blood that flows through it. Measuring local distortion of the artery wall is the first essential factor to evaluate in a ruptured artery. This paper aims to demonstrate the feasibility of this measure using MRI on a phantom of an abdominal aortic aneurysm (AAA) with realistic shape. The aortic geometry is obtained from a series of cine-MR images and reconstructed using Mimics software. From 4D flow and MRI measurements, the field of velocity is determined and introduced into a computational fluid dynamic (CFD) model to determine the mechanical boundaries applied on the wall artery (pressure and ultimately wall shear stress (WSS)). These factors are then converted into a solid model that enables wall deformations to be calculated. This approach was applied to a silicone phantom model of an AAA reconstructed from a patient's computed tomography-scan examination. The calculated deformations were then compared to those obtained in identical conditions by stereovision. The results of both methods were found to be close. Deformations of the studied AAA phantom with complex shape were obtained within a gap of 12% by modeling from MR data.

3 Tesla (1) H MR spectroscopy of hip bone marrow in a healthy population, assessment of normal fat content values and influence of age and sex.

PURPOSE: To evaluate in a healthy population normal spectroscopic fat content (FC) values of the hip bone marrow and to assess the influence of age and sex on bone marrow conversion. MATERIALS AND METHODS: Eighty volunteers (40 men; 40 women; ages: 20-60 years; divided into four consecutive groups) underwent acetabulum, femoral head, femoral neck, greater trochanter, and diaphysis localized (1) H MR spectroscopy. FC values of each anatomical site were obtained according to the following formula: Fat content = CH2 /(CH2 + Water)*100. To assess bone marrow conversion, a spectroscopic conversion index (SCI) was calculated as FC neck/FC greater trochanter. RESULTS: FC values showed a gradient as follows: greater trochanter > femoral head > femoral neck > diaphysis > acetabulum in every age group both in men and in women. SCI increased with age both in men and women, showing lower values in women for every age group. CONCLUSION: We obtained normal spectroscopic FC values from different areas of the hip, according to age and sex. These values may be used as reference values to evaluate, by the means of (1) H MR spectroscopy, pathological conditions affecting hip bone marrow.

Assessment of reduced field of view in diffusion tensor imaging of the lumbar nerve roots at 3 T.

OBJECTIVES: To assess the value of reduced field of view (rFOV) imaging in diffusion tensor imaging (DTI) and tractography of the lumbar nerve roots at 3 T from the perspective of future clinical trials. METHODS: DTI images of the lumbar nerves were obtained in eight healthy volunteers, with and without the rFOV technique. Non-coplanar excitation and refocusing pulses associated with outer volume suppression (OVS) were used to achieve rFOV imaging. Tractography was performed. A visual evaluation of image quality was made by two observers, both senior musculoskeletal radiologists. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in L5 and S1 roots. RESULTS: rFOV images of the L5 and S1 roots were assessed as being superior to full FOV (fFOV) images. Image quality was rated as good to excellent by both observers. Interobserver agreement was good. No significant difference was found in FA and ADC measurements of the L5 or S1 roots. On the contrary, only poor-quality images could be obtained with fFOV imaging as major artefacts were present. CONCLUSION: The rFOV approach was essential to achieve high-quality DTI imaging of lumbar nerve roots on 3-T MRI. KEY POINTS: • Diffusion tensor 3-T MR imaging of lumbar nerve roots creates severe artefacts. • A reduced field of view drastically reduces artefacts, thereby improving image quality. • Good-quality tractography images can even be obtained with rFOV imaging. • rFOV DTI is better than fFOV DTI for clinical studies.

Reproducibility of 1H MR spectroscopy of hip bone marrow at 3 Tesla.

PURPOSE: To assess the reproducibility of fat content (FC) values in five different anatomical areas of proximal femur by the means of (1)H 3 Tesla MR spectroscopy and to evaluate if any statistical difference exists when comparing right side to left side FC values in the same individual. MATERIALS AND METHODS: Thirty-three volunteers underwent unilateral (1)H MR spectroscopy of the hip. From 1 to 4 weeks later, they repeat the MR examination of the same hip to assess the reproducibility of the technique. Fifteen other volunteers underwent a bilateral (1)H MR hip spectroscopy to compare right and left side FC values. RESULTS: The reproducibility of (1)H MR spectroscopy was high in all the anatomic areas considered, ranging from 0.90 to 0.98. No statistically significant difference was found when the fat content values on the right side were compared to those on the left side. (P > 0.16). CONCLUSION: The 3 Tesla (1)H MR spectroscopy of hip bone marrow permitted highly reproducible fat content values in all the five anatomic areas examined. No statistical significant difference existed when comparing fat content values of the right side to those of the left side in the same individual.

Splitting of Pi and other ³¹P NMR anomalies of skeletal muscle metabolites in canine muscular dystrophy.

Many anomalies exist in the resting (31) P muscle spectra of boys with Duchenne muscular dystrophy (DMD) but few have been reported in Golden Retriever muscular dystrophy (GRMD), the closest existing animal model for DMD. Because GRMD is recommended for preclinical evaluation of therapies and quantitative outcome measures are needed, we investigated anomalies of (31) P NMRS in tibial cranial and biceps femoris muscles from 14 GRMD compared to 9 control (CONT) dogs. Alterations observed in DMD children - low phosphocreatine and high phospho-monoesters and -diesters - were all found in GRMD but increased pH was not. More surprisingly, inorganic phosphate (Pi) appeared to present a prominent splitting with an enhanced Pi(b) resonance at 0.3 ppm downfield of Pi(a) . Assuming that both resonances are Pi, the pH for Pi(a) in GRMD corresponded to a physiological intracellular pH(a) (6.97 ± 0.05), while pH(b) approached the extracellular range (7.27 ± 0.10) and correlated with pH(a) in GRMD (R(2) = 0.65). Both Pi(a) and Pi(b) were elevated compared to CONT and Pi(a) increased with age for GRMD (R(2) = 0.48, p < 0.001). Magnetisation transfer experiments between γATP and Pi were conducted to better characterise Pi pools. Equal T1 relaxation times for Pi(b) and Pi(a) did not support a mitochondrial origin of Pi(b) . We suggest that Pi(b) could originate from degenerating hypercontracted cells that have a leaky membrane and inadequate cell homeostasis and pH regulation. Pi(b) showed minimal chemical exchange in all dogs, while the exchange rate of Pi(a) was reduced in GRMD and might extraneously reflect low glycolytic activity in DMD. Taken together, the ensemble of (31) P NMRS alterations identifies muscle dysfunction and could provide useful biomarkers of therapeutic efficacy. Furthermore, among these, two might relate more specifically to dystrophic processes and merit further investigation: one is the existence of the enhanced alkaline Pi(b) pool; the other, mechanisms by which membrane disruption might increase phosphodiesters in dystrophy.

Investigating glycogenosis type III patients with multi-parametric functional NMR imaging and spectroscopy.

Debranching enzyme deficiency (Glycogen storage disease (GSD) type III) causes progressive muscle wasting myopathy. A comprehensive nuclear magnetic resonance study involving spectroscopy (NMRS) and imaging (NMRI) evaluated status and function of calf muscles in 18 GSDIII patients. At rest, (31)P NMRS showed elevated pH and accumulation of anomalous phosphomonoesters, (13)C NMRS quantified excess glycogen accumulation and NMRI demonstrated progressive fat replacement that paralleled muscle weakness. Multi-parametric functional NMR, performed at recovery from a single bout of aerobic exercise, simultaneously assessed oxidative phosphorylation from (31)P NMRS, muscle perfusion and BOLD, a marker of blood oxygenation, from arterial spin labeled NMRI, and oxygen uptake from deoxymyoglobin proton NMRS. While blocked glycogenolysis caused inadequate substrate supply to the mitochondria, combined measurements suggested that altered perfusion was also responsible for impaired post-exercise phosphocreatine recovery and could contribute to exercise intolerance in GSDIII. These non-invasive investigations provide new indices to quantify the progression of GSDIII.

Antioxidants and aging: NMR-based evidence of improved skeletal muscle perfusion and energetics.

We sought to examine the potential role of oxidative stress on skeletal muscle function with advancing age. Nuclear magnetic resonance (NMR) was employed to simultaneously assess muscle perfusion (arterial spin labeling) and energetics ((31)P NMR spectroscopy) in the lower leg of young (26 + or - 5 yr, n = 6) and older (70 + or - 5 yr, n = 6) healthy volunteers following the consumption of either placebo (PL) or an oral antioxidant (AO) cocktail (vitamins C and E and alpha-lipoic acid), previously documented to decrease plasma free radical concentration. NMR measurements were made during and after 5 min of moderate intensity (approximately 5 W) plantar flexion exercise. AO administration significantly improved end-exercise perfusion (AO, 50 + or - 5, and PL, 43 + or - 4 ml x 100 g(-1) x min(-1)) and postexercise perfusion area under the curve (AO, 1,286 + or - 236, and PL, 866 + or - 144 ml/100 g) in older subjects, whereas AO administration did not alter hemodynamics in the young group. Concomitantly, muscle oxidative capacity (time constant of phosphocreatine recovery, tau) was improved following AO in the older (AO, 43 + or - 1, and PL, 51 + or - 7 s) but not the young (AO, 54 + or - 5, and PL, 48 + or - 7 s) group. These findings support the concept that oxidative stress may be partially responsible for the age-related decline in skeletal muscle perfusion during physical activity and reveal a muscle metabolic reserve capacity in the elderly that is accessible under conditions of improved perfusion.

Multiparametric NMR-based assessment of skeletal muscle perfusion and metabolism during exercise in elderly persons: preliminary findings.

BACKGROUND: Aging is associated with a decline in exercise capacity that may be attributable to maladaptations in both skeletal muscle perfusion and metabolism; yet very little is known regarding the real-time, within-muscle interplay between these parameters during physical activity. Therefore, we utilized an unique nuclear magnetic resonance sequence to concomitantly examine changes in lower leg skeletal muscle perfusion and metabolism. METHODS: In young (26+/-5 years, n=6) and older (70+/-5 years, n=6) healthy volunteers, arterial spin labeling measurements of muscle perfusion were combined with 31 Phosphorous (31P) nuclear magnetic resonance spectroscopy to monitor high-energy phosphate metabolites during and after 5 minutes of moderate-intensity (approximately 5W) plantar flexion exercise. RESULTS: Compared with young, end-exercise perfusion was diminished in older participants (43+/-10 mL/100 g/minute, old; 60+/-7 mL/100 g.minute, young), accompanied by greater phosphocreatine (PCr) depletion (-28%+/-12%, old; -19%+/-7%, young) and elevated inorganic phosphate/PCr (0.41+/-0.2, old; 0.24+/-0.09, young); yet the time constant for PCr recovery (tau, an index of muscle oxidative capacity) was similar between groups (51+/-17 seconds, old; 48+/-7 seconds, young). CONCLUSIONS: Together, these preliminary data provide evidence of an age-related decline in tissue perfusion and increased "metabolic stress" during exercise but demonstrate that overall oxidative capacity in the elderly does not appear negatively affected by this relatively hypoperfused state.