T1rho Magnetic Resonance Imaging at 3T Detects Knee Cartilage Changes After Viscosupplementation.

Viscosupplementation may affect cartilage. Changes in T1rho magnetic resonance imaging (MRI) relaxation times correlate with proteoglycan changes in cartilage. The authors hypothesized that T1rho MRI will show an improvement in proteoglycan content at 6 weeks and 3 months after viscosupplementation and that this improvement will correlate with functional outcome scores. Ten patients (mean age, 56 years; Kellgren-Lawrence grade 1 or 2) underwent T1rho MRI at baseline, 6 weeks, and 3 months after viscosupplementation. Volumetric T1rho means were calculated by depth and region. Visual analog scale (VAS), International Knee Documentation Committee (IKDC), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were obtained. Mean T1rho values decreased in the superficial patella at 6 weeks (10.3%, P=.002) and 3 months (7.9%, P=.018) and in the middle patella at 6 weeks (7.0%, P=.014) compared with baseline values. Deep patella T1rho values increased at 3 months compared with 6 weeks (9.9%, P=.033), returning to values similar to baseline. Mean T1rho values increased in the deep tibia at 6 weeks (4.7%, P=.048) and in the middle tibia (5.2%, P=.004) and deep tibia (11.2%, P=.002) at 3 months compared with baseline. At 6 weeks, improvement was seen in VAS (5.9 to 3.9, P<.01), IKDC-9 (55.3 to 63.7, P=.03), and WOMAC (43.9 to 32.8, P=.03) scores. Functional VAS (4.0, P=.02), IKDC-9 (67.8, P=.04), and WOMAC (30.0, P=.04) scores remained better at 3 months. T1rho MRI is a feasible noninvasive method of studying molecular changes in cartilage. Some segments improved after viscosupplementation, and others worsened, possibly reflecting natural history or symptom relief and subsequent increase in activity-related wear.

Novel imaging of the intervertebral disk and pain.

T-1-rho (T1ρ) magnetic resonance imaging (MRI) and disc height ratio (DHR) are potential biomarkers of degenerative disk disease (DDD) related to biochemical composition and morphology of the intervertebral disk (IVD), respectively. To objectively detect DDD at an early stage, the hypothesis was tested that the average T1ρ relaxation time of the nucleus pulposus (NP) correlates with the disk height of degenerate IVDs, measured by MRI. Studies were performed on a 3-T Siemens Tim Trio clinical MRI scanner (Siemens Healthcare, Malvern, Pennsylvania, United States) on patients being treated for low back pain whose disks were categorized into (1) painful and (2) nonpainful subgroups based on provocative diskography and (3) age-matched healthy controls. Painful disks presented both low DHR and T1ρ values, nonpainful disks measured the highest DHR and extended to a higher range of T1ρ, and control disks presented a midrange DHR with the highest T1ρ values. T1ρ MRI evaluated in the NP of IVDs may be useful to establish a threshold (120 milliseconds here) above which indicates a healthy disk, and disks measuring low NP T1ρ (50 to 120 milliseconds here) would require disk height analysis to further categorize the disk. Combining T1ρ MRI and disk height analysis may hold promise in predicting painful disks without provocative diskography, and predictive models should be developed.

Quantitative cartilage degeneration associated with spontaneous osteoarthritis in a guinea pig model.

PURPOSE: To determine (i) the feasibility and intra- and inter-scan reproducibility of T(1ρ) MRI in assessing cartilage degeneration in a guinea pig model with naturally occurring joint disease that closely mimics human osteoarthritis (OA), (ii) demonstrate the sensitivity of T(1ρ) MRI in assessing the age dependent cartilage degeneration in OA progression as compared to histopathological changes. MATERIALS AND METHODS: Duncan-Hartley guinea pigs were obtained at various ages and maintained under an IACUC approved protocol. The left hind stifle joint was imaged using T(1ρ) MRI on a 9.4 Tesla Varian horizontal 20 cm bore scanner using a custom surface coil. Reproducibility of T(1ρ) MRI was assessed using 4-month-old guinea pigs (N = 3). Three age cohorts; 3 month (N = 8), 5 month (N = 6), and 9 month (N = 5), were used to determine the age-dependent osteoarthritic changes as measured by T(1ρ) MRI. Validation of age-dependent cartilage degeneration was confirmed by histology and Safranin-O staining. RESULTS: T(1ρ) values obtained in the cartilage of the stifle joint in guinea pigs were highly reproducible with an inter-scan mean coefficient of variation (CV) of 6.57% and a maximum intra-scan CV of 9.29%. Mean cartilage T(1ρ) values in animals with late stage cartilage degeneration were 56.3-56.9 ms (5-9 month cohorts) were both significantly (P < 0.01) higher than that obtained from 3-month-old cohort (44 ms) demonstrating an age-dependent variation. T(1ρ) was shown to be significantly greater than T(2) . T(1ρ) dispersion was observed in this animal model for the first time showing an increase of 45% between 500 Hz and 1500 Hz spin-locking frequency. Cartilage thickness measurements were calculated from single mid-coronal histology sections from same animals used for T(1ρ) MRI. Thickness calculations showed insignificant differences between 3- and 5-month cohorts and was significantly decreased by 9 months of age (P < 0.01). A moderate correlation (R(2) = 0.45) existed between T(1ρ) values and signal intensity of Safranin-O stain. CONCLUSION: The data presented demonstrate that T(1ρ) MRI is highly reproducible in this spontaneous model of OA and may serve as a noninvasive tool to characterize joint cartilage degeneration during OA. Age-dependent changes, verified with histological measurements of proteoglycan loss, correlated with T(1ρ) across different age groups. T(1ρ) has adequate dynamic range and is sensitive to detect and track the progression of cartilage degeneration in the guinea pig model before gross anatomical changes such as cartilage thinning has occurred. This study presents a technological advancement that would permit longitudinal studies of evaluating disease-modifying therapies useful for treating human OA.

T1ρ magnetic resonance imaging and discography pressure as novel biomarkers for disc degeneration and low back pain.

STUDY DESIGN: Prospective magnetic resonance imaging (MRI) study of patients low back pain (LBP) requiring discography as part of their routine clinical diagnoses and asymptomatic age-matched volunteers. OBJECTIVE: To determine whether T1ρ MRI and discography opening pressure (OP) are quantitative biomarkers of disc degeneration in LBP patients and in asymptomatic volunteers. SUMMARY OF BACKGROUND DATA: Disc degenerative disease, a common cause of LBP, is related to the patient's prognosis and serves as a target for therapeutic interventions. However, there are few quantitative measures in the clinical setting. Discography OP and T1ρ MRI are potential biomarkers of disc degenerative disease related to biochemical composition of the intervertebral disc. METHODS: The institutional review board approved all experiments, and informed consent was provided by each subject. Patients being treated for LBP (n = 17; 68 levels; mean age, 44 ± 6 years; and range, 30-53) and control subjects (n = 11; 44 levels; mean age, 43 ± 17 years; and range, 22-76) underwent T1ρ and T2 MRI on a Siemens 3T Tim Trio clinical scanner (Siemens Medical Solutions, Malvern, PA). The LBP patients also received multilevel provocative discography before their MRI. OP was recorded as the pressure when fluid first enters the nucleus of the intervertebral disc. RESULTS: T1ρ was significantly lower in the painful discs (55.3 ± 3.0 ms, mean ± SE) from control (92.0 ± 4.9 ms, P < 0.001) and nonpainful discs (83.6 ± 3.2 ms, P < 0.001). Mean OP for the painful discs (11.8 ± 1.0 psi, mean ± SE) was significantly lower than that for nonpainful discs (19.1 ± 0.7 psi, P < 0.001). Both T1ρ and OP correlated moderately with Pfirrmann degenerative grade. Receiver-operating-characteristic area under the curve was 0.91 for T1ρ MRI and 0.84 for OP for predicting painful discs. CONCLUSION: T1ρ and OP are quantitative measures of degeneration that are consistent across both control subjects and LBP patients. A significant and strong correlation exists between T1ρ values and in vivo OP measurements obtained by discography in LBP patients.

T(1ρ) MRI in Alzheimer's disease: detection of pathological changes in medial temporal lobe.

BACKGROUND: The need of an early and noninvasive diagnosis of AD requires the development of imaging-based techniques. As an alternative, the magnetic resonance image (MRI) relaxation time constant (T1ρ) was measured in brains of Alzheimer's disease (AD), mild-cognitive impairment (MCI), and age-matched controls in order to determine whether T1ρ values correlated with the neurological diagnosis. METHODS: MRI was performed on AD (n=48), MCI (n=45), and age-matched control (n=41), on a 1.5 Tesla Siemens clinical MRI scanner. T1ρ maps were generated by fitting each pixel's intensity as a function of the duration of the spin-lock pulse. T1ρ values were calculated from the gray matter (GM) and white matter (WM) of medial temporal lobe (MTL). RESULTS: GM and WM T1ρ values were 87.5±1.2 ms and 80.5±1.4 ms, respectively, in controls, 90.9±1.3 ms and 84.1±1.7 ms in MCI, and 91.9±.8 ms and 88.3±1.3 ms in AD cohorts. Compared to control, AD patients showed 9% increased WM T1ρ and 5% increased GM T1ρ. Compared to control, MCI individuals showed 4% increased T1ρ both in WM and GM. A 5% increased T1ρ was found in WM of AD over MCI. CONCLUSION: The increased T1ρ in WM and GM of MTL in AD may be associated with the pathological changes that are not evident on conventional MRI.

Validation of sodium magnetic resonance imaging of intervertebral disc.

STUDY DESIGN: This study demonstrated the diagnostic potential of sodium (Na) magnetic resonance imaging (MRI) for noninvasive quantification of proteoglycan (PG) in the intervertebral discs. OBJECTIVE: To determine the existence of a linear correlation between intervertebral disc [Na] measured from sodium MRI and [PG] measurement from DMMB assay. SUMMARY OF BACKGROUND DATA: Previous studies have shown the possibility of quantifying Na in vivo using sodium MRI, however, none has shown a direct linear correlation between Na measured from sodium MRI and in the invertebral discs. METHODS: Three-dimensional sodium MRI images of bovine discs were acquired and converted into [Na] maps. Samples were systematically removed from the discs for DMMB assay. The removal locations were photographically recorded and applied to the [Na] maps to extract the [Na] measurements for comparison. In vivo sodium MRI scans were also carried out on a pair of symptomatic and asymptomatic subjects. RESULTS: The linear regression fit of [Na] versus [PG] data yielded a significant linear correlation coefficient of 0.71. The in vivo sodium MRI image of the symptomatic subject showed significant [Na] decrease when compared to that of the asymptomatic subject. CONCLUSION: Specificity of sodium MRI for PG in the intervertebral discs makes it a promising diagnostic tool for the earlier phase of disc degeneration.

Early marker for Alzheimer's disease: hippocampus T1rho (T(1rho)) estimation.

PURPOSE: To evaluate the T1rho (T(1rho)) MRI relaxation time in hippocampus in the brain of Alzheimer's disease (AD), mild cognitive impairment (MCI), and control, and to determine whether the T(1rho) shows any significant difference between these cohorts. MATERIALS AND METHODS: With informed consent, AD (n = 49), MCI (n = 48), and age-matched control (n = 31) underwent T(1rho) MRI on a Siemens 1.5T Scanner. T(1rho) values were automatically calculated from the left and right hippocampus region using in-house developed software. Bonferroni post-hoc multiple comparisons was performed to compare the T(1rho) value among the different cohorts. RESULTS: Significantly higher T(1rho) values were observed both in AD (P = 0.000) and MCI (P = 0.037) cohorts compared to control; also, the T(1rho) in AD was significantly high over (P = 0.032) MCI. Hippocampus T(1rho) was 13% greater in the AD patients than control, while in MCI it was 7% greater than control. Hippocampus T(1rho) in AD patients was 6% greater than MCI. CONCLUSION: Higher hippocampus T(1rho) values in the AD patients might be associated with the increased plaques burden. A follow-up study would help to determine the efficacy of T(1rho) values as a predictor of developing AD in the control and MCI individuals.

Cross-molecular coupling in combined photoassociation and Feshbach resonances.

We model combined photoassociation and Feshbach resonances in a Bose-Einstein condensate. When the magnetic field is far-off resonance, cross coupling between the two target molecules--enabled by the shared dissociation continuum--leads to an anomalous dispersive shift in the position of laser resonance, as well as unprecedented elimination and enhancement of resonant photoassociation via quantum interference. For off-resonant lasers, a dispersive shift and quantum interference appear similarly in resonant three-body Feshbach losses, except that the Feshbach node is tunable with intensity.

T1rho-prepared balanced gradient echo for rapid 3D T1rho MRI.

PURPOSE: To develop a T1rho-prepared, balanced gradient echo (b-GRE) pulse sequence for rapid three-dimensional (3D) T1rho relaxation mapping within the time constraints of a clinical exam (<10 minutes), examine the effect of acquisition on the measured T1rho relaxation time and optimize 3D T1rho pulse sequences for the knee joint and spine. MATERIALS AND METHODS: A pulse sequence consisting of inversion recovery-prepared, fat saturation, T1rho-preparation, and b-GRE image acquisition was used to obtain 3D volume coverage of the patellofemoral and tibiofemoral cartilage and lower lumbar spine. Multiple T1rho-weighted images at various contrast times (spin-lock pulse duration [TSL]) were used to construct a T1rho relaxation map in both phantoms and in the knee joint and spine in vivo. The transient signal decay during b-GRE image acquisition was corrected using a k-space filter. The T1rho-prepared b-GRE sequence was compared to a standard T1rho-prepared spin echo (SE) sequence and pulse sequence parameters were optimized numerically using the Bloch equations. RESULTS: The b-GRE transient signal decay was found to depend on the initial T1rho-preparation and the corresponding T1rho map was altered by variations in the point spread function with TSL. In a two compartment phantom, the steady state response was found to elevate T1rho from 91.4+/-6.5 to 293.8+/-31 and 66.9+/-3.5 to 661+/-207 with no change in the goodness-of-fit parameter R2. Phase encoding along the longest cartilage dimension and a transient signal decay k-space filter retained T1rho contrast. Measurement of T1rho using the T1rho-prepared b-GRE sequence matches standard T1rho-prepared SE in the medial patellar and lateral patellar cartilage compartments. T1rho-preparedb-GRE T1rho was found to have low interscan variability between four separate scans. Mean patellar cartilage T1rho was elevated compared to femoral and tibial cartilage T1rho. CONCLUSION: The T1rho-prepared b-GRE acquisition rapidly and reliably accelerates T1rho quantification of tissues offset partially by a TSL-dependent point spread function.