Unsaturation level decreased in bone marrow fat of postmenopausal women with low bone density using high resolution magic angle spinning (HRMAS) 1H NMR spectroscopy.

There are increasing evidences suggesting bone marrow adiposity tissue (MAT) plays a critical role in affecting both bone quantity and quality. However, very limited studies that have investigated the association between the composition of MAT and bone mineral density (BMD). The goal of this study was to quantify MAT unsaturation profile of marrow samples from post-menopausal women using ex vivo high-resolution magic angle spinning (HRMAS) proton nuclear magnetic resonance (1H NMR) spectroscopy, and to investigate the relationship between MAT composition and BMD. Bone marrow samples were obtained by iliac crest aspiration during surgical procedures from 24 postmenopausal women (65-89years) who had hip surgery due to bone fracture or arthroplasty. Marrow fat composition parameters, in particular, unsaturation level (UL), mono-unsaturation level (MUL) and saturation level (SL), were quantified using HRMAS 1H NMR spectroscopy. The patients were classified into three groups based on the DXA BMD T-scores: controls, osteopenia and osteoporosis. Marrow fat composition was compared between these three groups as well as between subjects with and without factures using ANOCOVA, adjusted for age. Subjects with lower BMD (n=17) had significantly lower MUL (P=0.003) and UL (P=0.039), and significantly higher SL (P=0.039) compared to controls (n=7). When separating lower BMD into osteopenia (n=9) and osteoporosis (n=8) groups, subjects with osteopenia had significantly lower MUL (P=0.002) and UL (P=0.010), and significantly higher SL (P=0.010) compared to healthy controls. No significant difference was observed between subjects with osteopenia and osteoporosis. Using HRMAS 1H NMR, significantly lower unsaturation and significantly higher saturation levels were observed in the marrow fat of subjects with lower BMD. HRMAS 1H NMR was shown to be a powerful tool for identifying novel MR markers of marrow fat composition that are associated with bone quality and potentially fracture, and other bone pathologies and changes after treatment. A better understanding of the relationship between bone marrow composition and bone quality in humans may identify novel treatment targets, and provide guidance on novel interventions and therapeutic strategies for bone preservation.

Quantification of bone marrow water and lipid composition in anterior cruciate ligament-injured and osteoarthritic knees using three-dimensional magnetic resonance spectroscopic imaging.

PURPOSE: To quantitatively evaluate longitudinal changes in water and lipid in knee bone marrow with and without bone marrow edema-like lesions (BMELs) in subjects with acutely ruptured anterior cruciate ligaments (ACLs) or osteoarthritis (OA) using three-dimensional magnetic resonance spectroscopic imaging (3D MRSI). MATERIAL AND METHODS: Ten ACL and 10 OA subjects who presented with BMEL and seven BMEL-free controls were scanned at 3T. All ACL and OA subjects had one-year follow-up scans. 3D MRSI was acquired in BMEL and adjacent bone marrow, and water content (WC) and unsaturated lipid index (UI) were calculated in each region of interest. RESULTS: At baseline, ACL BMEL WC was significantly higher than ACL non-BMEL, OA BMEL, and control WC; ACL non-BMEL WC, ACL BMEL UI, and OA BMEL WC were significantly higher than control. ACL BMEL WC decreased significantly one year post-reconstruction; UI decreased non-significantly (p=0.09). No significant changes in OA BMEL or ACL and OA non-BMEL WC and UI were observed. CONCLUSION: 3D MRSI is a powerful method of quantitatively assessing the biochemical composition of bone marrow in OA and ACL-injured knees, which may serve as imaging markers to improve comprehension of primary and secondary OA pathology.

Simultaneous acquisition of T1ρ and T2 quantification in knee cartilage: repeatability and diurnal variation.

PURPOSE: To develop a robust sequence that combines T1ρ and T2 quantifications and to examine the in vivo repeatability and diurnal variation of T1ρ and T2 quantifications in knee cartilage. MATERIALS AND METHODS: Six healthy volunteers were scanned in the morning and afternoon on 2 days using a combined T1ρ and T2 quantification sequence developed in this study. Repeatability of T1ρ and T2 quantification was estimated using root-mean-square coefficients-of-variation (RMS-CV). T1ρ and T2 values from morning scans were compared to those from afternoon scans using paired t-tests. RESULTS: The overall RMS-CV of in vivo T1ρ and T2 quantification was 5.3% and 5.2%, respectively. The RMS-CV of am scans was 4.2% and 5.0% while the RMS-CV of pm scans was 6.0% and 6.3% for T1ρ and T2 , respectively. No significant difference was found between T1ρ or T2 values in the morning and in the afternoon. CONCLUSION: A sequence that combines T1ρ and T2 quantification with scan time less than 10 minutes and is robust to B0 and B1 inhomogeneity was developed with excellent repeatability. For a cohort with low-level daily activity, although no significant diurnal variation of cartilage MR relaxation times was observed, the afternoon scans had inferior repeatability compared to morning scans.

Vertebral bone marrow fat associated with lower trabecular BMD and prevalent vertebral fracture in older adults.

CONTEXT: Bone marrow fat (BMF) and bone mineral density (BMD) by dual x-ray energy absorptiometry (DXA) are negatively correlated. However, little is known about the association of BMF with fracture or with separate trabecular and cortical bone compartments. OBJECTIVE: Our objective was to assess the relationships between vertebral BMF, BMD by quantitative computed tomography, and fracture in older adults. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional study in the Age Gene/Environment Susceptibility-Reykjavik cohort. MAIN OUTCOME MEASURES: Outcomes measures included vertebral BMF (L1-L4) measured with magnetic resonance spectroscopy, quantitative computed tomography and DXA scans of the hip and spine, and DXA vertebral fracture assessments. Previous clinical fracture was determined from medical records. RESULTS: In 257 participants without recent bone-active medication use, mean age was 79 (SD 3.1) years. Mean BMF was 53.5% ± 8.1% in men and 55.0% ± 8.4% in women. Those with prevalent vertebral fracture (21 men, 32 women) had higher mean BMF in models adjusted for BMD. In separate models by sex, the difference was statistically significant only in men (57.3% vs 52.8%, P = 0.02). BMF was associated with lower trabecular volumetric BMD (vBMD) at the spine (-10.5% difference for each 1 SD increase in BMF, P < 0.01), total hip, and femoral neck, but not with cortical vBMD, in women. In men, BMF was marginally associated with trabecular spine vBMD (-6.1%, P = 0.05). Total hip and spine areal BMD (aBMD) were negatively correlated with BMF in women only. CONCLUSION: Higher marrow fat correlated with lower trabecular, but not cortical, BMD in older women but not men. Higher marrow fat was associated with prevalent vertebral fracture in men, even after adjustment for BMD.

High-resolution magic angle spinning NMR spectroscopy of human osteoarthritic cartilage.

Osteoarthritis (OA) is a degenerative disease of the joints and results in changes in the biochemical composition of cartilage. Previous studies have been undertaken that have used high-resolution NMR spectroscopy to study the biochemical composition of porcine, canine and bovine cartilage. In the present study, high-resolution magical angle spinning (HR-MAS) NMR spectroscopy at 11.7 T has been used to characterize metabolites and detect differences in the spectral signature of human knee articular cartilage from non-OA healthy cadaver knees and samples acquired from severe OA patients at the time of total knee replacement surgery. A statistically significant difference in the alanine (1.47 p.p.m.), N-acetyl (2.04 p.p.m.), choline (3.25 p.p.m.) and glycine (3.55 p.p.m.) metabolite levels was observed between healthy and OA specimens. The results of the present study indicate that a decrease in the intensity of N-acetyl resonance occurs in the later stages of OA. A positive correlation of the N-acetyl levels as measured by (1)H HR-MAS NMR spectroscopy with the total proteoglycan content in the same cartilage specimens as measured by the glycosaminoglycan (GAG) assay was observed. This indicates that N-acetyl can serve as an important bio-marker of OA disease progression. A decrease in the alanine concentration in OA may be attributed to the degradation of the collagen framework with disease progression and eventual loss of the degradation products that are transported from cartilage into the synovial cavity.

A novel variable field system for field-cycled dynamic nuclear polarization spectroscopy.

Dynamic nuclear polarization (DNP) is an NMR-based technique which enables detection and spectral characterization of endogenous and exogenous paramagnetic substances measured via transfer of polarization from the saturated unpaired electron spin system to the NMR active nuclei. A variable field system capable of performing DNP spectroscopy with NMR detection at any magnetic field in the range 0-0.38 T is described. The system is built around a clinical open-MRI system. To obtain EPR spectra via DNP, partial cancellation of the detection field B(0)(NMR) is required to alter the evolution field B(0)(EPR) at which the EPR excitation is achieved. The addition of resistive actively shielded field cancellation coils in the gap of the primary magnet provides this field offset in the range of 0-100 mT. A description of the primary magnet, cancellation coils, power supplies, interfacing hardware, RF electronics and console are included. Performance of the instrument has been evaluated by acquiring DNP spectra of phantoms with aqueous nitroxide solutions (TEMPOL) at three NMR detection fields of 97 G, 200 G and 587 G corresponding to 413 kHz, 851.6 kHz and 2.5 MHz respectively and fixed EPR evolution field of 100 G corresponding to an irradiation frequency of 282.3 MHz. This variable-field DNP system offers great flexibility for the performance of DNP spectroscopy with independent optimum choice of EPR excitation and NMR detection fields.

Variable Field Proton-Electron Double-Resonance Imaging: Application to pH mapping of aqueous samples.

A new concept of Variable Field Proton-Electron Double-Resonance Imaging (VF PEDRI) is proposed. This allows for functional mapping using specifically designed paramagnetic probes (e.g. oxygen or pH mapping) with MRI high quality spatial resolution and short acquisition time. Studies performed at 200 G field MRI with phantoms show that a pH map of the sample can be extracted using only two PEDRI images acquired in 140 s at pre-selected EPR excitation fields providing pH resolution of 0.1 pH units and a spatial resolution of 1.25mm. Note that while concept of functional VF PEDRI was demonstrated using the pH probe, it can be applied for studies of other biologically relevant parameters of the medium such as redox state, concentrations of oxygen or glutathione using specifically designed EPR probes.

Real-time calculation and visualization of spectra in field-cycled dynamic nuclear polarization spectroscopy.

Field-cycled dynamic nuclear polarization (FC-DNP), which is based on the Overhauser effect, provides a new way to perform in vivo measurements of free radicals in biological systems. Since it measures the alterations of the nuclear magnetic resonance (NMR) signal in the presence of paramagnetic molecules, a customized program is usually needed in FC-DNP experiments to extract spectral information from the acquired NMR signals. While this program can be designed to calculate the spectrum after all the NMR signals are collected, the batch-processing mode inevitably causes delay and is not convenient for in vivo applications. In this paper, we report the development of a real-time DNP spectrum calculation and visualization program, called RT_DNP, for FC-DNP experiments. A dynamic data exchange (DDE) client was implemented to enable real-time receipt of the system information and the NMR signals from a commercial NMR console. The received NMR signals and experimental parameters were then used to calculate the DNP spectrum during the data acquisition. The real-time DNP spectrum calculation and visualization program was tested in experiments. A seamless integration of the program into a commercial NMR console has been achieved.

Proton electron double resonance imaging of free radical distribution in environmental science applications--first results and perspectives.

In this contribution, we explore the potential of proton electron double resonance imaging (PEDRI) in environmental science (hydrogeological) applications. After a discussion of the hydrogeological motivation for studies of free radical transport in environmental matrices, we present results from first experiments that show the principal applicability of the PEDRI technique to sediment samples. Field-cycled (FC) relaxation time contrast is identified as a possible source of artifacts in samples in which strong concentration gradients of the free radical phase are present. Furthermore, an outlook is given on how PEDRI can help in observations of the local interplay among contaminants, water and nonaqueous liquid phases.