Accuracy and repeatability of QRAPMASTER and MRF-vFA.

Our purpose is to evaluate bias and repeatability of the quantitative MRI sequences QRAPMASTER, based on steady-state imaging, and variable Flip Angle MRF (MRF-VFA), based on the transient response. Both techniques are assessed with a standardized phantom and five volunteers on 1.5 T and 3 T clinical scanners. All scans were repeated eight times in consecutive weeks. In the phantom, the mean bias±95% confidence interval for T1 values with QRAPMASTER was 10 ± 10% on 1.5 T and 4 ± 13% on 3.0 T. The mean bias for T1 values with MRF-vFA was 21 ± 17% on 1.5 T and 9 ± 9% on 3.0 T. For T2 values the mean bias with QRAPMASTER was 12 ± 3% on 1.5 T and 23 ± 1% on 3.0 T. For T2 values the mean bias with MRF-vFA was 17 ± 1% on 1.5 T and 19 ± 2% on 3.0 T. QRAPMASTER estimated lower T1 and T2 values than MRF-vFA. Repeatability was good with low coefficients of variation (CoV). Mean CoV ± 95% confidence interval for T1 were 3.2 ± 0.4% on 1.5 T and 4.5 ± 0.8% on 3.0 T with QRAPMASTER and 2.7% ± 0.2% on 1.5 T and 2.5 ± 0.2% on 3.0 T with MRF-vFA. For T2 were 3.3 ± 1.9% on 1.5 T and 3.2 ± 0.6% on 3.0 T with QRAPMASTER and 2.0 ± 0.4% on 1.5 T and 5.7 ± 1.0% on 3.0 T with MRF-vFA. The in-vivo T1 and T2 are in the range of values previously reported by other authors. The in-vivo mean CoV ± 95% confidence interval in gray matter were for T1 1.7 ± 0.2% using QRAPMASTER and 0.7 ± 0.5% using MRF-vFA and for T2 were 0.9 ± 0.4% using QRAPMASTER and 2.4 ± 0.5% using MRF-vFA. In white matter were for T1 0.9 ± 0.3% using QRAPMASTER and 1.3 ± 1.1% using MRF-vFA and for T2 were 0.7 ± 0.4% using QRAPMASTER and 2.4 ± 0.4% using MRF-vFA. A GLM analysis showed that the variations in T1 and T2 mainly depend on the field strength and the subject, but not on the follow-up repetition in different days. This confirms the high repeatability of QRAPMASTER and MRF-vFA. In summary, QRAPMASTER and MRF-vFA on both systems were highly repeatable with moderate accuracy, providing results comparable to standard references. While repeatability was similar for both methods, QRAPMASTER was more accurate. QRAPMASTER is a tested commercial product but MRF-vFA is 4.77 times faster, which would ease the inclusion of quantitative relaxometry.

From signal-based to comprehensive magnetic resonance imaging.

We present and evaluate a new insight into magnetic resonance imaging (MRI). It is based on the algebraic description of the magnetization during the transient response-including intrinsic magnetic resonance parameters such as longitudinal and transverse relaxation times (T1, T2) and proton density (PD) and experimental conditions such as radiofrequency field (B1) and constant/homogeneous magnetic field (B0) from associated scanners. We exploit the correspondence among three different elements: the signal evolution as a result of a repetitive sequence of blocks of radiofrequency excitation pulses and encoding gradients, the continuous Bloch equations and the mathematical description of a sequence as a linear system. This approach simultaneously provides, in a single measurement, all quantitative parameters of interest as well as associated system imperfections. Finally, we demonstrate the in-vivo applicability of the new concept on a clinical MRI scanner.

Computed Tomography and Magnetic Resonance Imaging.

Imaging in Oncology is rapidly moving from the detection and size measurement of a lesion to the quantitative assessment of metabolic processes and cellular and molecular interactions. Increasing insights into cancer as a complex disease with involvement of the tumor stroma in tumor pathobiological processes have made it clear that for successful control of cancer, treatment strategies should not only be directed at the cancer cells but should also take aspects of the tumor microenvironment into account. This requires an understanding of the complex molecular and cellular interactions in cancer tissue. Recent developments in imaging technology have increased the possibility to image various pathobiological processes in cancer development and response to treatment. For computed tomography (CT) and magnetic resonance imaging (MRI) various improvements in hardware, software, and imaging probes have lifted these modalities from classical anatomical imaging techniques to techniques suitable to image and quantify various physiological processes and molecular and cellular interactions. Next to a more general overview of possible imaging targets in oncology, this chapter provides an overview of the various developments in CT and MRI technology and some specific applications.

Implementation and validation of ASL perfusion measurements for population imaging.

PURPOSE: Pseudocontinuous arterial spin labeling (pCASL) allows for noninvasive measurement of regional cerebral blood flow (CBF), which has the potential to serve as biomarker for neurodegenerative and cardiovascular diseases. This work aimed to implement and validate pCASL on the dedicated MRI system within the population-based Rotterdam Study, which was installed in 2005 and for which software and hardware configurations have remained fixed. METHODS: Imaging was performed on two 1.5T MRI systems (General Electric); (I) the Rotterdam Study system, and (II) a hospital-based system with a product pCASL sequence. An in-house implementation of pCASL was created on scanner I. A flow phantom and three healthy volunteers (<27 years) were scanned on both systems for validation purposes. The data of the first 30 participants (86 ± 4 years) of the Rotterdam Study undergoing pCASL scans on scanner I only were analyzed with and without partial volume correction for gray matter. RESULTS: The validation study showed a difference in blood flow velocity, sensitivity, and spatial coefficient of variation of the perfusion-weighted signal between the two scanners, which was accounted for during post-processing. Gray matter CBF for the Rotterdam Study participants was 52.4 ± 8.2 ml/100 g/min, uncorrected for partial volume effects of gray matter. In this elderly cohort, partial volume correction for gray matter had a variable effect on measured CBF in a range of cortical and sub-cortical regions of interest. CONCLUSION: Regional CBF measurements are now included to investigate novel biomarkers in the Rotterdam Study. This work highlights that when it is not feasible to purchase a novel ASL sequence, an in-house implementation is valuable.

Tissue-Specific T2 * Biomarkers in Patellar Tendinopathy by Subregional Quantification Using 3D Ultrashort Echo Time MRI.

BACKGROUND: Quantitative MRI of patellar tendinopathy (PT) can be challenging due to spatial variation of T2 * relaxation times. PURPOSE: 1) To compare T2 * quantification using a standard approach with analysis in specific tissue compartments of the patellar tendon. 2) To evaluate test-retest reliability of different methods for fitting ultrashort echo time (UTE)-relaxometry data. STUDY TYPE: Prospective. SUBJECTS: Sixty-five athletes with PT. FIELD STRENGTH/SEQUENCE: 3D UTE scans covering the patellar tendon were acquired using a 3.0T scanner and a 16-channel surface coil. ASSESSMENT: Voxelwise median T2 * was quantified with monoexponential, fractional-order, and biexponential fitting. We applied two methods for T2 * analysis: first, a standard approach by analyzing all voxels covering the proximal patellar tendon. Second, within subregions of the patellar tendon, by using thresholds on biexponential fitting parameter percentage short T2 * (0-30% for mostly long T2 *, 30-60% for mixed T2 *, and 60-100% for mostly short T2 *). STATISTICAL TESTS: Average test-retest reliability was assessed in three athletes using coefficients-of-variation (CV) and coefficients-of-repeatability (CR). RESULTS: With standard image analysis, we found a median [interquartile range, IQR] monoexponential T2 * of 6.43 msec [4.32-8.55] and fractional order T2 * 4.39 msec [3.06-5.78]. The percentage of short T2 * components was 52.9% [35.5-69.6]. Subregional monoexponential T2 * was 13.78 msec [12.11-16.46], 7.65 msec [6.49-8.61], and 3.05 msec [2.52-3.60] and fractional order T2 * 11.82 msec [10.09-14.44], 5.14 msec [4.25-5.96], and 2.19 msec [1.82-2.64] for 0-30%, 30-60%, and 60-100% short T2 *, respectively. Biexponential component short T2 * was 1.693 msec [1.417-2.003] for tissue with mostly short T2 * and long T2 * of 15.79 msec [13.47-18.61] for mostly long T2 *. The average CR (CV) was 2 msec (15%), 2 msec (19%) and 10% (22%) for monoexponential, fractional order and percentage short T2 *, respectively. DATA CONCLUSION: Patellar tendinopathy is characterized by regional variability in binding states of water. Quantitative multicompartment T2 * analysis in PT can be facilitated using a voxel selection method based on using biexponential fitting parameters. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1 J. Magn. Reson. Imaging 2020;52:420-430.

Quantitative subchondral bone perfusion imaging in knee osteoarthritis using dynamic contrast enhanced MRI.

OBJECTIVE: Subchondral bone changes, characterized by increased bone turnover and vascularity, are believed to stimulate progression and pain in knee osteoarthritis (OA). The objective of this study was to evaluate the bone perfusion in knee OA using quantitative dynamic contrast enhanced MRI (DCE-MRI). DESIGN: Unicompartmental knee OA patients were included and underwent 3 Tesla DCE-MRI and T2-weighted MRI. Quantitative DCE-MRI analysis of Ktrans and Kep, representing perfusion parameters, was performed to evaluate differences between the most and least affected knee compartment. First, DCE-MRI parameter differences between epimetaphyseal and subchondral bone in both femur and tibia were assessed. Second, DCE-MRI parameters in subchondral bone marrow lesions (BMLs) were compared to surrounding subchondral bone without BMLs. RESULTS: Twenty-three patients were analyzed. Median Ktrans and Kep in epimetaphyseal bone were significantly higher (p < 0.05) in the most affected (Ktrans: 0.014; Kep: 0.054 min-1) compared to least affected (Ktrans: 0.010; Kep: 0.016 min-1) compartment. For subchondral bone, DCE-MRI parameters were significantly higher (p < 0.05) in the most affected (Ktrans: 0.019; Kep: 0.091 min-1) compared to least affected (Ktrans: 0.014; Kep: 0.058 min-1) compartment as well. Subchondral BMLs detected on fat-saturated T2-weighted images were present in all patients. Median Ktrans (0.091 vs 0.000 min-1) and Kep (0.258 vs 0.000 min-1) were significantly higher within subchondral BMLs compared to surrounding subchondral bone without BMLs (p < 0.001). CONCLUSIONS: Increased perfusion parameters in epimetaphyseal bone, subchondral bone and BMLs are observed in unicompartmental knee OA. BMLs likely account for most of the effect of the higher bone perfusion in knee OA.

Comparison of four MR carotid surface coils at 3T.

BACKGROUND: The quality of carotid wall MRI can benefit substantially from a dedicated RF coil that is tailored towards the human neck geometry and optimized for image signal-to-noise ratio (SNR), parallel imaging performance and RF penetration depth and coverage. In last decades, several of such dedicated carotid coils were introduced. However, a comparison of the more successful designs is still lacking. OBJECTIVE: To perform a head-to-head comparison over four dedicated MR carotid surface coils with 4, 6, 8 and 30 coil elements, respectively. MATERIAL AND METHODS: Ten volunteers were scanned on a 3T scanner. For each subject, multiple black-blood carotid vessel wall images were measured using the four coils with different parallel imaging settings. The performance of the coils was evaluated and compared in terms of image coverage, penetration depth and noise correlations between elements. Vessel wall of a common carotid section was delineated manually. Subsequently, images were assessed based on vessel wall morphology and image quality parameters. The morphological parameters consisted of the vessel wall area, thickness, and normalized wall index (wall area/total vessel area). Image quality parameters consisted of vessel wall SNR, wall-lumen contrast-to-noise ratio (CNR), the vessel g-factor, and CNRindex ((wall-lumen signal) / (wall+lumen signal)). Repeated measures analysis of variance (rmANOVA) was applied for each parameter for the averaged 10 slices for all volunteers to assess effect of coil and SENSE factor. If the rmANOVA was significant, post-hoc comparisons were conducted. RESULTS: No significant coil effect were found for vessel wall morphological parameters. SENSE acceleration affected some morphological parameters for 6- and 8-channel coils, but had no effect on the 30-channel coil. The 30-channel coil achieved high acceleration factors (10x) with significantly lower vessel g-factor values (ps ≤ 0.01), but lower vessel wall SNR and CNR values (ps ≤ 0.01). CONCLUSION: All four coils were capable of high-quality carotid MRI. The 30-channel coil is recommended when rapid image acquisition acceleration is required for 3D measurements, whereas 6- and 8-channel coils demonstrated the highest SNR performance.

Blood perfusion of patellar bone measured by dynamic contrast-enhanced MRI in patients with patellofemoral pain: A case-control study.

BACKGROUND: Altered perfusion might play an important role in the pathophysiology of patellofemoral pain (PFP), a common knee complaint with unclear pathophysiology. PURPOSE: To investigate differences in dynamic contrast-enhanced (DCE)-MRI perfusion parameters between patients with PFP and healthy control subjects. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Thirty-five adult patients with PFP and 44 healthy adult control subjects. FIELD STRENGTH/SEQUENCE: 3T DCE-MRI consisting of a sagittal, anterior-posterior, frequency-encoded, fat-suppressed 3D spoiled gradient-echo sequence with intravenous contrast administration. ASSESSMENT: Patellar bone volumes of interest (VOIs) were delineated by a blinded observer. Quantitative perfusion parameters (kep and ktrans ) were calculated from motion-compensated DCE-MRI data by fitting Tofts' model. Weighted mean and unweighted median values of kep and ktrans were computed within the patellar bone VOIs. STATISTICAL TESTS: Differences in patellar bone perfusion parameters were compared between groups by linear regression analyses, adjusted for confounders. RESULTS: Mean differences of weighted mean and unweighted median were 0.0039 (95% confidence interval [CI] -0.0013; 0.0091) and 0.0052 (95% CI -0.0078; 0.018) for ktrans , and 0.046 (95% CI -0.021; 0.11) and 0.069 (95% CI -0.017; 0.15) for kep , respectively. All perfusion parameters were not significantly different between groups (P-values: 0.32; 0.47 for ktrans , and 0.24; 0.15) for kep . However, a significant difference in variance between populations was observed for ktrans (P-value 0.007). DATA CONCLUSION: Higher patellar bone perfusion parameters were found in patients with PFP when compared to healthy control subjects, but these differences were not statistically significant. This result, and the observed significant difference in ktrans variance, warrant further research. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1344-1350.

Is T1ρ Mapping an Alternative to Delayed Gadolinium-enhanced MR Imaging of Cartilage in the Assessment of Sulphated Glycosaminoglycan Content in Human Osteoarthritic Knees? An in Vivo Validation Study.

PURPOSE: To determine if T1ρ mapping can be used as an alternative to delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in the quantification of cartilage biochemical composition in vivo in human knees with osteoarthritis. MATERIALS AND METHODS: This study was approved by the institutional review board. Written informed consent was obtained from all participants. Twelve patients with knee osteoarthritis underwent dGEMRIC and T1ρ mapping at 3.0 T before undergoing total knee replacement. Outcomes of dGEMRIC and T1ρ mapping were calculated in six cartilage regions of interest. Femoral and tibial cartilages were harvested during total knee replacement. Cartilage sulphated glycosaminoglycan (sGAG) and collagen content were assessed with dimethylmethylene blue and hydroxyproline assays, respectively. A four-dimensional multivariate mixed-effects model was used to simultaneously assess the correlation between outcomes of dGEMRIC and T1ρ mapping and the sGAG and collagen content of the articular cartilage. RESULTS: T1 relaxation times at dGEMRIC showed strong correlation with cartilage sGAG content (r = 0.73; 95% credibility interval [CI] = 0.60, 0.83) and weak correlation with cartilage collagen content (r = 0.40; 95% CI: 0.18, 0.58). T1ρ relaxation times did not correlate with cartilage sGAG content (r = 0.04; 95% CI: -0.21, 0.28) or collagen content (r = -0.05; 95% CI = -0.31, 0.20). CONCLUSION: dGEMRIC can help accurately measure cartilage sGAG content in vivo in patients with knee osteoarthritis, whereas T1ρ mapping does not appear suitable for this purpose. Although the technique is not completely sGAG specific and requires a contrast agent, dGEMRIC is a validated and robust method for quantifying cartilage sGAG content in human osteoarthritis subjects in clinical research.

Three-dimensional quantitative T1 and T2 mapping of the carotid artery: Sequence design and in vivo feasibility.

PURPOSE: A novel three-dimensional (3D) T1 and T2 mapping protocol for the carotid artery is presented. METHODS: A 3D black-blood imaging sequence was adapted allowing carotid T1 and T2 mapping using multiple flip angles and echo time (TE) preparation times. B1 mapping was performed to correct for spatially varying deviations from the nominal flip angle. The protocol was optimized using simulations and phantom experiments. In vivo scans were performed on six healthy volunteers in two sessions, and in a patient with advanced atherosclerosis. Compensation for patient motion was achieved by 3D registration of the inter/intrasession scans. Subsequently, T1 and T2 maps were obtained by maximum likelihood estimation. RESULTS: Simulations and phantom experiments showed that the bias in T1 and T2 estimation was < 10% within the range of physiological values. In vivo T1 and T2 values for carotid vessel wall were 844 ± 96 and 39 ± 5 ms, with good repeatability across scans. Patient data revealed altered T1 and T2 values in regions of atherosclerotic plaque. CONCLUSION: The 3D T1 and T2 mapping of the carotid artery is feasible using variable flip angle and variable TE preparation acquisitions. We foresee application of this technique for plaque characterization and monitoring plaque progression in atherosclerotic patients.

Magnetic Resonance Detection of CD34+ Cells from Umbilical Cord Blood Using a 19F Label.

Impaired homing and delayed recovery upon hematopoietic stem cell transplantation (HSCT) with hematopoietic stem cells (HSC) derived from umbilical cord blood (UCB) is a major problem. Tracking transplanted cells in vivo will be helpful to detect impaired homing at an early stage and allows early interventions to improve engraftment and outcome after transplantation. In this study, we show sufficient intracellular labeling of UCB-derived CD34+ cells, with 19F-containing PLGA nanoparticles which were detectable with both flow cytometry and magnetic resonance spectroscopy (MRS). In addition, labeled CD34+ cells maintain their capacity to proliferate and differentiate, which is pivotal for successful engraftment after transplantation in vivo. These results set the stage for in vivo tracking experiments, through which the homing efficiency of transplanted cells can be studied.

Assessment of elastin deficit in a Marfan mouse aneurysm model using an elastin-specific magnetic resonance imaging contrast agent.

BACKGROUND: Ascending aortic dissection and rupture remain a life-threatening complication in patients with Marfan syndrome. The extracellular matrix provides strength and elastic recoil to the aortic wall, thereby preventing radial expansion. We have previously shown that ascending aortic aneurysm formation in Marfan mice (Fbn1(C1039G/+)) is associated with decreased aortic wall elastogenesis and increased elastin breakdown. In this study, we test the feasibility of quantifying aortic wall elastin content using MRI with a gadolinium-based elastin-specific magnetic resonance contrast agent in Fbn1(C1039G/+) mice. METHODS AND RESULTS: Ascending aorta elastin content was measured in 32-week-old Fbn1(C1039G/+) mice and wild-type (n=9 and n=10, respectively) using 7-T MRI with a T1 mapping sequence. Significantly lower enhancement (ie, lower R1 values, where R1=1/T1) was detected post-elastin-specific magnetic resonance contrast agent in Fbn1(C1039G/+) compared with wild-type ascending aortas (1.15±0.07 versus 1.36±0.05; P<0.05). Post-elastin-specific magnetic resonance contrast agent R1 values correlated with ascending aortic wall gadolinium content directly measured by inductively coupled mass spectroscopy (P=0.006). CONCLUSIONS: Herein, we demonstrate that MRI with elastin-specific magnetic resonance contrast agent accurately measures elastin bound gadolinium within the aortic wall and detects a decrease in aortic wall elastin in Marfan mice compared with wild-type controls. This approach has translational potential for noninvasively assessing aneurysm tissue changes and risk, as well as monitoring elastin content in response to therapeutic interventions.

Delayed gadolinium-enhanced MRI of the meniscus (dGEMRIM) in patients with knee osteoarthritis: relation with meniscal degeneration on conventional MRI, reproducibility, and correlation with dGEMRIC.

OBJECTIVES: To assess (1) whether normal and degenerated menisci exhibit different T1GD on delayed gadolinium-enhanced MRI of the meniscus (dGEMRIM), (2) the reproducibility of dGEMRIM and (3) the correlation between meniscus and cartilage T1GD in knee osteoarthritis (OA) patients. METHODS: In 17 OA patients who underwent dGEMRIM twice within 7 days, meniscus and cartilage T1GD was calculated. Meniscus pathology was evaluated on conventional MRI. T1GD in normal and degenerated menisci were compared using a Student's t-test. Reproducibility was assessed using ICCs. Pearson's correlation was calculated between meniscus and cartilage T1GD. RESULTS: A trend towards lower T1GD in degenerated menisci (mean: 402 ms; 95% CI: 359-444 ms) compared to normal menisci (mean: 448 ms; 95% CI: 423-473 ms) was observed (p = 0.05). Meniscus T1GD ICCs were 0.85-0.90. The correlation between meniscus and cartilage T1GD was moderate in the lateral (r = 0.52-0.75) and strong in the medial compartment (r = 0.78-0.94). CONCLUSIONS: Our results show that degenerated menisci have a clear trend towards lower T1GD compared to normal menisci. Since these results are highly reproducible, meniscus degeneration may be assessed within one delayed gadolinium-enhanced MRI simultaneously with cartilage. The strong correlation between meniscus and cartilage T1GD suggests concomitant degeneration in both tissues in OA, but also suggests that dGEMRIC may not be regarded entirely as sulphated glycosaminoglycan specific. KEY POINTS: dGEMRIM T1 GD can possibly be used to assess meniscal degeneration; dGEMRIM yields highly reproducible meniscal T1 GD in early stage osteoarthritic patients; Concomitant degeneration of cartilage and meniscus tissue occurs in early stage osteoarthritis; dGEMRIC cannot be regarded as entirely sulphated glycosaminoglycan specific.

Exploration of MR-guided head and neck hyperthermia by phantom testing of a modified prototype applicator for use with proton resonance frequency shift thermometry.

Magnetic resonance thermometry (MRT) offers non-invasive temperature imaging and can greatly contribute to the effectiveness of head and neck hyperthermia. We therefore wish to redesign the HYPERcollar head and neck hyperthermia applicator for simultaneous radio frequency (RF) heating and magnetic resonance thermometry. In this work we tested the feasibility of this goal through an exploratory experiment, in which we used a minimally modified applicator prototype to heat a neck model phantom and used an MR scanner to measure its temperature distribution. We identified several distorting factors of our current applicator design and experimental methods to be addressed during development of a fully MR compatible applicator. To allow MR imaging of the electromagnetically shielded inside of the applicator, only the lower half of the HYPERcollar prototype was used. Two of its antennas radiated a microwave signal (150 W, 434 MHz) for 11 min into the phantom, creating a high gradient temperature profile (ΔTmax = 5.35 °C). Thermal distributions were measured sequentially, using drift corrected proton resonance frequency shift-based MRT. Measurement accuracy was assessed using optical probe thermometry and found to be about 0.4 °C (0.1-0.7 °C). Thermal distribution size and shape were verified by thermal simulations and found to have a good correlation (r(2 )= 0.76).

Validation of MR thermometry: method for temperature probe sensor registration accuracy in head and neck phantoms.

PURPOSE: Magnetic resonance thermometry (MRT) is an attractive means to non-invasively monitor in vivo temperature during head and neck hyperthermia treatments because it can provide multi-dimensional temperature information with high spatial resolution over large regions of interest. However, validation of MRT measurements in a head and neck clinical set-up is crucial to ensure the temperature maps are accurate. Here we demonstrate a unique approach for temperature probe sensor localisation in head and neck hyperthermia test phantoms. METHODS: We characterise the proton resonance frequency shift temperature coefficient and validate MRT measurements in an oil-gel phantom by applying a combination of MR imaging and 3D spline fitting for accurate probe localisation. We also investigate how uncertainties in both the probe localisation and the proton resonance frequency shift (PRFS) thermal coefficient affect the registration of fibre-optic reference temperature probe and MRT readings. RESULTS: The method provides a two-fold advantage of sensor localisation and PRFS thermal coefficient calibration. We provide experimental data for two distinct head and neck phantoms showing the significance of this method as it mitigates temperature probe localisation errors and thereby increases accuracy of MRT validation results. CONCLUSIONS: The techniques presented here may be used to simplify calibration experiments that use an interstitial heating device, or any heating method that provides rapid and spatially localised heat distributions. Overall, the experimental verification of the data registration and PRFS thermal coefficient calibration technique provides a useful benchmarking method to maximise MRT accuracy in any similar context.

T1 mapping in the rat myocardium at 7 tesla using a modified CINE inversion recovery sequence.

PURPOSE: To evaluate the reproducibility and sensitivity of the modified CINE inversion recovery (mCINE-IR) acquisition on rats for measuring the myocardial T1 at 7 Tesla. MATERIALS AND METHODS: The recently published mCINE-IR acquisition on humans was applied on rats for the first time, enabling the possibility of translational studies with an identical sequence. Simulations were used to study signal evolution and heart rate dependency. Gadolinium phantoms, a heart specimen and a healthy rat were used to study reproducibility. Two cryo-infarcted rats were scanned to measure late gadolinium enhancement (LGE). RESULTS: In the phantom reproducibility studies the T1 measurements had a maximum coefficient of variation (COV) of 1.3%. For the in vivo reproducibility the COV was below 5% in the anterior cardiac segments. In simulations with phantoms and specimens, a heart rate dependency of approximately 0.5 ms/bpm was present. The T1 maps of the cryo-infarcted rats showed a clear lowering of T1 in de LGE region. CONCLUSION: The results show that mCINE-IR is highly reproducible and that the sensitivity allows detecting T1 changes in the rat myocardium.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) shows no change in cartilage structural composition after viscosupplementation in patients with early-stage knee osteoarthritis.

INTRODUCTION: Viscosupplementation with hyaluronic acid (HA) of osteoarthritic (OA) knee joints has a well-established positive effect on clinical symptoms. This effect, however, is only temporary and the working mechanism of HA injections is not clear. It was suggested that HA might have disease modifying properties because of its beneficial effect on cartilage sulphated glycosaminoglycan (sGAG) content. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a highly reproducible, non-invasive surrogate measure for sGAG content and hence composition of cartilage. The aim of this study was to assess whether improvement in cartilage structural composition is detected using dGEMRIC 14 weeks after 3 weekly injections with HA in patients with early-stage knee OA. METHODS: In 20 early-stage knee OA patients (KLG I-II), 3D dGEMRIC at 3T was acquired before and 14 weeks after 3 weekly injections with HA. To evaluate patient symptoms, the knee injury and osteoarthritis outcome score (KOOS) and a numeric rating scale (NRS) for pain were recorded. To evaluate cartilage composition, six cartilage regions in the knee were analyzed on dGEMRIC. Outcomes of dGEMRIC, KOOS and NRS before and after HA were compared using paired t-testing. Since we performed multiple t-tests, we applied a Bonferroni-Holm correction to determine statistical significance for these analyses. RESULTS: All KOOS subscales ('pain', 'symptoms', 'daily activities', 'sports' and 'quality of life') and the NRS pain improved significantly 14 weeks after Viscosupplementation with HA. Outcomes of dGEMRIC did not change significantly after HA compared to baseline in any of the cartilage regions analyzed in the knee. CONCLUSIONS: Our results confirm previous findings reported in the literature, showing persisting improvement in symptomatic outcome measures in early-stage knee OA patients 14 weeks after Viscosupplementation. Outcomes of dGEMRIC, however, did not change after Viscosupplementation, indicating no change in cartilage structural composition as an explanation for the improvement of clinical symptoms.

In vivo quantitative assessment of cell viability of gadolinium or iron-labeled cells using MRI and bioluminescence imaging.

In cell therapy, noninvasive monitoring of in vivo cell fate is challenging. In this study we investigated possible differences in R1, R2 or R2* relaxation rate as a measure of overall cell viability for mesenchymal stem cells labeled with Gd-liposomes (Gd-MSCs) or iron oxide nanoparticles (SPIO-MSCs). Cells were also transduced with a luciferase vector, facilitating a correlation between MRI findings and cell viability using bioluminescence imaging (BLI). Viable Gd-MSCs were clearly distinguishable from nonviable Gd-MSCs under both in vitro and in vivo conditions, clearly differing quantitatively (ΔR1 and ΔR2) as well as by visual appearance (hypo- or hyperintense contrast). Immediately post-injection,viable Gd-MSCs caused a substantially larger ΔR2 and lower ΔR1 effect compared with nonviable MSCs. With time, the ΔR1 and ΔR2 relaxation rate showed a good negative correlation with increasing cell number following proliferation. Upon injection, no substantial quantitative or visual differences between viable and nonviable SPIO-MSCs were detected. Moreover, nonviable SPIO-MSCs caused a persisting signal void in vivo, compromising the specificity of this contrast agent. In vivo persistence of SPIO particles was confirmed by histological staining. A large difference was found between SPIO- and Gd-labeled cells in the accuracy of MR relaxometry in assessing the cell viability status. Gd-liposomes provide a more accurate and specific assessment of cell viability than SPIO particles. Viable Gd cells can be differentiated from nonviable Gd cells even by visual interpretation. These findings clearly indicate Gd to be the favourable contrast agent in qualitative and quantitative evaluation of labeled cell fate in future cell therapy experiments.

Image registration improves human knee cartilage T1 mapping with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC).

OBJECTIVES: To evaluate the effect of automated registration in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of the knee on the occurrence of movement artefacts on the T1 map and the reproducibility of region-of-interest (ROI)-based measurements. METHODS: Eleven patients with early-stage knee osteoarthritis and ten healthy controls underwent dGEMRIC twice at 3 T. Controls underwent unenhanced imaging. ROIs were manually drawn on the femoral and tibial cartilage. T1 calculation was performed with and without registration of the T1-weighted images. Automated three-dimensional rigid registration was performed on the femur and tibia cartilage separately. Registration quality was evaluated using the square root Cramér-Rao lower bound (CRLB(σ)). Additionally, the reproducibility of dGEMRIC was assessed by comparing automated registration with manual slice-matching. RESULTS: Automated registration of the T1-weighted images improved the T1 maps as the 90% percentile of the CRLB(σ) was significantly (P < 0.05) reduced with a median reduction of 55.8 ms (patients) and 112.9 ms (controls). Manual matching and automated registration of the re-imaged T1 map gave comparable intraclass correlation coefficients of respectively 0.89/0.90 (patients) and 0.85/0.85 (controls). CONCLUSIONS: Registration in dGEMRIC reduces movement artefacts on T1 maps and provides a good alternative to manual slice-matching in longitudinal studies.

Cell quantification: evolution of compartmentalization and distribution of iron-oxide particles and labeled cells.

The purpose of the study was to show the feasibility of quantification in the case of cell death, cell migration and cell division by parametric MRI. We identify limitations for quantitative cell tracking owing to mixed parallel processes. Various intravoxel SPIO-labeled cell, super paramagnetic iron oxide particles (SPIO) and micron-sized paramagnetic iron oxide (MPIO) particle distributions were prepared by methods mimicking biologically relevant processes (compartmentalization, migration, division and cell death). R(2)* and R(2) relaxometry measurements were performed at 3.0 T; iron concentration was measured by optical emission spectrometry. The effects of spatial distribution and compartmentalization of paramagnetic iron-oxide particles on relaxivity were analyzed. Assessment of R(2)' (R(2)*-R(2)) allowed differentiation between intracellular and extracellular SPIO only if no high-iron-content extracellular particles were present. Relaxivity was sensitive to variations in cell labeling. Samples of the same cell types embedded in the same suspension media at the same cell density produced different relaxivity values, depending on the preparation of the labeled cells. In the case of cell division, a unique relationship between relaxation rate and iron concentration was found, where the relaxivity proved to be independent of initial cell labeling. In case of cell mixing, the cell density could be derived from relaxation values, even if iron concentration was undetermined. We demonstrated that relaxometry does not allow labeled cell quantification when multiple physiological processes such as cell division and cell migration coexist. The measured transversal relaxation rates were sensitive to the labeling technique. However, under special circumstances, despite the numerous limiting factors, quantification of the number of labeled cells by relaxometry was feasible.