In osteomalacia decreased mineralization reduces the stiffness and static strength of bone. We hypothesized that hypomineralization in osteomalacic bone could be quantified by solidstate 31 Osteomalacia (rickets) is a disease characterized by hypomineralization of bone (1). Among the various causes of hypomineralization is a deficiency of vitamin D, calcium, and phosphorus resulting from inadequate nutrition, renal failure, or interference of certain drugs with calcium and vitamin D metabolism (2). Hypomineralization implies a reduced mineral mass per unit volume of bone tissue (also referred to as the degree of mineralization of bone (DMB) (3)). Both the stiffness and compressive strength of bone are largely determined by its mineral content, which in the normal skeleton is very tightly regulated. Currey (4) showed that even small variations in mineral content can have a disproportionately large influence on breaking strength, and noted that the latter decreased threefold for a decrease in ash content (mineral content) from 70% to 63%. Hypomineralization thus results in impaired mechanical competence of the skeleton and therefore increased fracture risk. Evaluation of the DMB requires knowledge about both bone mass and bone volume. The most common modalities used in the diagnosis of bone disease-dual-energy X-ray absorptiometry (DEXA) and X-ray computed tomography (CT)-cannot distinguish between osteoporosis (i.e., a reduced amount of normally mineralized bone) and osteomalacia (a normal amount of undermineralized bone) because these techniques measure only the apparent density as the amount of mineral mass per unit area (or volume, respectively) of tissue. While several destructive methods for measuring true mineral density (gravimetric analysis, microradiography, chemical analysis, etc.) are available, there is currently no noninvasive modality for measuring the DMB.Magnetic resonance imaging (MRI) offers a unique opportunity for noninvasive quantification of bone mineral whose major constituent is a poorly crystalline nonstoichiometric calcium phosphate similar in composition to low-crystalline hydroxyapatite, Ca 10 (OH) 2 (PO 4 ) 6 . The feasibility of imaging 31 P by solid-state MRI (SS-MRI) was recently demonstrated in bone specimens (5,6) as well as in vivo (7,8). However, there has been no demonstration so far that differences in mineralization density can be detected in bone disease. Quantification of phosphorus by MRI is complicated by the lower magnetic moment and unfavorable relaxation properties of the 31 P nucleus. The absence of rapid molecular motions in solids results in extremely short transverse relaxation times (8) and long spin-lattice relaxation times (9), both of which adversely affect the SNR.The purpose of the present work was to explore the feasibility of using 31 P solid-state MRI to quantify phosphorus with sufficient precision to distinguish between osteomalacic and normally mineralized bone in a rabbit model of osteomalacia. Toward this objective we designed and implemented a 3D ...

In this work we hypothesize that bisphosphonate treatment following ovariectomy manifests in increased phosphorus and decreased water concentration, both quantifiable nondestructively with ultra-short echo-time (UTE) 31P and 1H MRI techniques. We evaluated this hypothesis in ovariectomized (OVX) rats undergoing treatment with two regimens of alendronate. Sixty female four-month old rats divided into four groups of 15 animals each: ovariectomized (OVX), OVX treatment groups ALN1 and ALN2, receiving 5μg/kg/day and 25μg/kg/day of alendronate, and a sham-operated group (NO) serving as control. Treatment, starting one week post surgery, lasted for 50 days at which time animals were sacrificed. Whole bones from the left and right femora were extracted from all the animals. 31P and 1H water concentration were measured by UTE MRI at 162 and 400 MHz in the femoral shaft and the results compared with other measures of mineral and matrix properties obtained by 31P solution NMR, CT density, ash weight, and water measured by dehydration. Mechanical parameters (elastic modulus, EM, and ultimate strength, US) were obtained by three-point bending. The following quantities were lower in OVX relative to NO: phosphorus concentration measured by 31P-MRI (−8%; 11.4±0.9 vs 12.4±0.8 %, p <0.005), 31P-NMR (−4%; 12.8±0.4 vs 13.3±0.8 %, p<0.05) and μ-CT density (−2.5%; 1316±34 vs 1349±32 mg/cm3, p=0.005). In contrast, water concentration by 1H-MRI was elevated in OVX relative to NO (+6%; 15.5±1.7 vs 14.6±1.4 %, p<0.05). Alendronate treatment increased phosphorus concentration and decreased water concentration in a dose-dependent manner, the higher dose yielding significant changes relative to values found in OVX animals: 31P-MRI (+14%; p<0.0001), 31P-NMR (+9%; p<0.0001), ash content (+1.5%; p<0.005), μ-CT mineralization density (+2.8%; p<0.05), 1H-MRI, (−19%, p<0.0001). The higher dose raised phosphorus concentration above and water concentration below NO levels: 31P-MRI (+6%; p<0.05), 31P-NMR (+5%; p=0.01), ash content (+1.5%; p=0.005), 1H-MRI (−14%; p<0.0001), drying water (−10%; p<0.0005). Finally, the group means of phosphorus concentration were positively correlated with EM and US (R2≥0.98, p<0.001 to p<0.05) even though the pooled data from individual animals were not. The results highlight the implications of estrogen depletion and bisphosphonate treatment on mineral composition and mechanical properties and the potential of solid-state MR imaging to detect these changes in situ in an animal model of rat ovariectomy.

Purpose-To investigate the magnetic field dependence of the signal-to-noise ratio (SNR) for carotid vessel wall magnetic resonance imaging (MRI) using phased-array (PA) surface coils by comparing images obtained at 1.5 T and 3 T, and to determine to what extent the improved SNR at the higher field can be traded for improved spatial resolution.Materials and methods-Two pairs of dual-element PA coils were constructed for operation at the two field strengths. The individual elements of each PA were matched to 50 Ω impedance on the neck and tuned at the respective frequencies. The coils were evaluated on a cylindrical phantom positioned with its axis parallel to the main field, and with the coils placed on either side of the phantom parallel to the sagittal plane. In-vivo MR images of the carotid arteries were obtained in five subjects at both field strengths with a fast spin-echo double-inversion black-blood pulse sequence with fat saturation. SNR was measured at both field strengths using standard techniques.Results-At a depth corresponding to the average location of the carotid arteries in the study subjects, mean phantom SNR for the two coils was higher at 3 T by a factor of 2.5. The greater than linear increase is due to only partial coil loading of these relatively small coils. The practically achievable average SNR gain in vivo was 2.1. The lower in vivo SNR gain is attributed to a reduction in T 2 and prolongation of T 1 at the higher field strength and, to a lesser extent, the requirement for reduced refocusing pulse flip angle to operate within specific absorption ratio limits. The superior SNR at 3 T appears to provide considerably improved vessel wall delineation.Conclusions-Carotid artery vessel wall MRI using phased-array surface coils provides a considerable increase in SNR when field strength is raised from 1.5 T to 3 T. This increase can be traded for enhanced in-plane resolution.

Osteomalacia is characterized by hypomineralization of the bone associated with increased water content. In this work we evaluate the hypotheses that 1) 3D solid-state magnetic resonance imaging (MRI) of (31)P (SSI-PH) and (1)H (SSI-WATER) of cortical bone can quantify the key characteristics of osteomalacia induced by low-phosphate diet; and 2) return to normophosphatemic diet (NO) results in recovery of these indices to normal levels. Twenty female five-week old rabbits were divided into four groups. Five animals were fed a normal diet for 8 weeks (NOI); five a hypophosphatemic diet (0.09%) for the same period to induce osteomalacia (HYI). To examine the effect of recovery from hypophosphatemia an additional five animals received a hypophosphatemic diet for 8 weeks, after which they were returned to a normal diet for 6 weeks (HYII). Finally, five animals received a normal diet for the entire 14 weeks (NOII). The NOI and HYI animals were sacrificed after 8 weeks, the NOII and HYII groups after 14 weeks. Cortical bone was extracted from the left and right tibiae of all the animals. Water content was measured by SSI-WATER and by a previously reported spectroscopic proton-deuteron nuclear magnetic resonance (NMR) exchange technique (NMR-WATER), phosphorus content by SSI-PH. All MRI and NMR experiments were performed on a 9.4 T spectroscopy/micro-imaging system. Degree of mineralization of bone (DMB) was measured by micro-CT and elastic modulus and ultimate strength by 3-point bending. The following parameters were lower in the hypophosphatemic group: phosphorus content measured by SSI-PH (9.5+/-0.4 versus 11.1+/-0.3 wt.%, p<0.0001), ash content (63.9+/-1.7 versus 65.4+/-1.1 wt.%, p=0.05), ultimate strength, (96.3+/-16.0 versus 130.7+/-6.4 N/mm(2), p=0.001), and DMB (1115+/-28 versus 1176+/-24 mg/cm(3), p=0.003); SSI-WATER: 16.1+/-1.5 versus 14.4+/-1.1 wt.%, p=0.04; NMR-WATER: 19.0+/-0.6 versus 17.4+/-1.2 wt.%, p=0.01. Return to a normophosphatemic diet reduced or eliminated these differences (SSI-PH: 9.5+/-0.9 versus 10.6+/-0.8 wt.%, p=0.04; DMB: 1124+/-31 versus 1137+/-10 mg/cm(3), p=0.2; US: 95.6+/-18.6 versus 103.9+/-7.5 N/mm(2), p=0.2; SSI-WATER: 12.4+/-0.6 versus 12.2+/-0.3 wt.%, p=0.3) indicating recovery of the mineral density close to normal levels. Phosphorus content measured by SSI-PH was significantly correlated with DMB measured by micro-CT (r(2)=0.47, p=0.001) as well as with ultimate strength (r(2)=0.54, p=0.0004). The results show that the methods presented have potential for in situ assessment of mineralization and water, both critical to the bone's mechanical behavior.