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Background: Early changes in breast intratumor heterogeneity during neoadjuvant chemotherapy may reflect the tumor's ability to adapt and evade treatment. We investigated the combination of precision medicine predictors of genomic and MRI data towards improved prediction of recurrence free survival (RFS)., Methods: A total of 100 women from the ACRIN 6657/I-SPY 1 trial were retrospectively analyzed. We estimated MammaPrint, PAM50 ROR-S, and p53 mutation scores from publicly available gene expression data and generated four, voxel-wise 3-D radiomic kinetic maps from DCE-MR images at both pre- and early-treatment time points. Within the primary lesion from each kinetic map, features of change in radiomic heterogeneity were summarized into 6 principal components., Results: We identify two imaging phenotypes of change in intratumor heterogeneity (p < 0.01) demonstrating significant Kaplan-Meier curve separation (p < 0.001). Adding phenotypes to established prognostic factors, functional tumor volume (FTV), MammaPrint, PAM50, and p53 scores in a Cox regression model improves the concordance statistic for predicting RFS from 0.73 to 0.79 (p = 0.002)., Conclusions: These results demonstrate an important step in combining personalized molecular signatures and longitudinal imaging data towards improved prognosis., (© 2023. The Author(s).)

Purpose: Image registration plays a vital role in spatially aligning multiple MRI scans for better longitudinal assessment of tumor morphological features. The objective was to evaluate the effect of registration accuracy of six established deformable registration methods(ANTs, DRAMMS, ART, NiftyReg, SSD-FFD, and NMI-FFD) on the predictive value of extracted radiomic features when modeling recurrence-free-survival(RFS) for women after neoadjuvant chemotherapy(NAC) for locally advanced breast cancer., Methods: 130 women had DCE-MRI scans available from the first two visits in the ISPY1/ACRIN-6657 cohort. We calculated the transformation field from each of the different deformable registration methods, and used it to compute voxel-wise parametric-response-maps(PRM) for established four kinetic features.104-radiomic features were computed from each PRM map to characterize intra-tumor heterogeneity. We evaluated performance for RFS using Cox-regression, C-statistic, and Kaplan-Meier(KM) plots., Results: A baseline model(F1:Age, Race, and Hormone-receptor-status) had a 0.54 C-statistic, and model F2(baseline + functional-tumor-volume at early treatment visit(FTV 2 )) had 0.63. The F2+ANTs had the highest C-statistic(0.72) with the smallest landmark differences(5.40±4.40mm) as compared to other models. The KM curve for model F2 gave p=0.004 for separation between women above and below the median hazard compared to the model F1(p=0.31). A models augmented with radiomic features, also achieved significant KM curve separation(p<0.001) except the F2+ART model., Conclusion: Incorporating image registration in quantifying changes in tumor heterogeneity during NAC can improve prediction of RFS. Radiomic features of PRM maps derived from warping the DCE-MRI kinetic maps using ANTs registration method further improved the early prediction of RFS as compared to other methods., (Copyright © 2022. Published by Elsevier Inc.)

We analyzed DCE-MR images from 132 women with locally advanced breast cancer from the I-SPY1 trial to evaluate changes of intra-tumor heterogeneity for augmenting early prediction of pathologic complete response (pCR) and recurrence-free survival (RFS) after neoadjuvant chemotherapy (NAC). Utilizing image registration, voxel-wise changes including tumor deformations and changes in DCE-MRI kinetic features were computed to characterize heterogeneous changes within the tumor. Using five-fold cross-validation, logistic regression and Cox regression were performed to model pCR and RFS, respectively. The extracted imaging features were evaluated in augmenting established predictors, including functional tumor volume (FTV) and histopathologic and demographic factors, using the area under the curve (AUC) and the C-statistic as performance measures. The extracted voxel-wise features were also compared to analogous conventional aggregated features to evaluate the potential advantage of voxel-wise analysis. Voxel-wise features improved prediction of pCR (AUC = 0.78 (±0.03) vs 0.71 (±0.04), p < 0.05 and RFS (C-statistic = 0.76 ( ± 0.05), vs 0.63 ( ± 0.01)), p < 0.05, while models based on analogous aggregate imaging features did not show appreciable performance changes (p > 0.05). Furthermore, all selected voxel-wise features demonstrated significant association with outcome (p < 0.05). Thus, precise measures of voxel-wise changes in tumor heterogeneity extracted from registered DCE-MRI scans can improve early prediction of neoadjuvant treatment outcomes in locally advanced breast cancer.

Although the role of cancer-activated stroma in malignant progression has been well investigated, the influence of an activated stroma in therapy response is not well understood. Using retrospective pilot cohorts, we previously observed that MRI detected stromal contrast enhancement was associated with proximity to the tumor and was predictive for relapse-free survival in patients with breast cancer receiving neoadjuvant chemotherapy. Here, to evaluate the association of stromal contrast enhancement to therapy, we applied an advanced tissue mapping technique to evaluate stromal enhancement patterns within 71 patients enrolled in the I-SPY 1 neoadjuvant breast cancer trial. We correlated MR stromal measurements with stromal protein levels involved in tumor progression processes. We found that stromal percent enhancement values decrease with distance from the tumor edge with the estimated mean change ranging [Formula: see text] to [Formula: see text] ([Formula: see text]) for time points T2 through T4. While not statistically significant, we found a decreasing trend in global stromal signal enhancement ratio values with the use of chemotherapy. There were no statistically significant differences between MR enhancement measurements and stromal protein levels. Findings from this study indicate that stromal features characterized by MRI are impacted by chemotherapy and may have predictive value in a larger study.

Previous research has shown that system-dependent gradient nonlinearity (GNL) introduces a significant spatial bias (nonuniformity) in apparent diffusion coefficient (ADC) maps. Here, the feasibility of centralized retrospective system-specific correction of GNL bias for quantitative diffusion-weighted imaging (DWI) in multisite clinical trials is demonstrated across diverse scanners independent of the scanned object. Using corrector maps generated from system characterization by ice-water phantom measurement completed in the previous project phase, GNL bias correction was performed for test ADC measurements from an independent DWI phantom (room temperature agar) at two offset locations in the bore. The precomputed three-dimensional GNL correctors were retrospectively applied to test DWI scans by the central analysis site. The correction was blinded to reference DWI of the agar phantom at magnet isocenter where the GNL bias is negligible. The performance was evaluated from changes in ADC region of interest histogram statistics before and after correction with respect to the unbiased reference ADC values provided by sites. Both absolute error and nonuniformity of the ADC map induced by GNL (median, 12%; range, -35% to +10%) were substantially reduced by correction (7-fold in median and 3-fold in range). The residual ADC nonuniformity errors were attributed to measurement noise and other non-GNL sources. Correction of systematic GNL bias resulted in a 2-fold decrease in technical variability across scanners (down to site temperature range). The described validation of GNL bias correction marks progress toward implementation of this technology in multicenter trials that utilize quantitative DWI.

Purpose: Characterize system-specific bias across common magnetic resonance imaging (MRI) platforms for quantitative diffusion measurements in multicenter trials., Methods: Diffusion weighted imaging (DWI) was performed on an ice-water phantom along the superior-inferior (SI) and right-left (RL) orientations spanning ± 150 mm. The same scanning protocol was implemented on 14 MRI systems at seven imaging centers. The bias was estimated as a deviation of measured from known apparent diffusion coefficient (ADC) along individual DWI directions. The relative contributions of gradient nonlinearity, shim errors, imaging gradients, and eddy currents were assessed independently. The observed bias errors were compared with numerical models., Results: The measured systematic ADC errors scaled quadratically with offset from isocenter, and ranged between -55% (SI) and 25% (RL). Nonlinearity bias was dependent on system design and diffusion gradient direction. Consistent with numerical models, minor ADC errors (± 5%) due to shim, imaging and eddy currents were mitigated by double echo DWI and image coregistration of individual gradient directions., Conclusion: The analysis confirms gradient nonlinearity as a major source of spatial DW bias and variability in off-center ADC measurements across MRI platforms, with minor contributions from shim, imaging gradients and eddy currents. The developed protocol enables empiric description of systematic bias in multicenter quantitative DWI studies., (© 2015 Wiley Periodicals, Inc.)

Purpose: To evaluate the ability of various software (SW) tools used for quantitative image analysis to properly account for source-specific image scaling employed by magnetic resonance imaging manufacturers., Methods: A series of gadoteridol-doped distilled water solutions (0%, 0.5%, 1%, and 2% volume concentrations) was prepared for manual substitution into one (of three) phantom compartments to create "variable signal," whereas the other two compartments (containing mineral oil and 0.25% gadoteriol) were held unchanged. Pseudodynamic images were acquired over multiple series using four scanners such that the histogram of pixel intensities varied enough to provoke variable image scaling from series to series. Additional diffusion-weighted images were acquired of an ice-water phantom to generate scanner-specific apparent diffusion coefficient (ADC) maps. The resulting pseudodynamic images and ADC maps were analyzed by eight centers of the Quantitative Imaging Network using 16 different SW tools to measure compartment-specific region-of-interest intensity., Results: Images generated by one of the scanners appeared to have additional intensity scaling that was not accounted for by the majority of tested quantitative image analysis SW tools. Incorrect image scaling leads to intensity measurement bias near 100%, compared to nonscaled images., Conclusion: Corrective actions for image scaling are suggested for manufacturers and quantitative imaging community.

Background: Clinical scores of mammographic breast density are highly subjective. Automated technologies for mammography exist to quantify breast density objectively, but the technique that most accurately measures the quantity of breast fibroglandular tissue is not known., Purpose: To compare the agreement of three automated mammographic techniques for measuring volumetric breast density with a quantitative volumetric MRI-based technique in a screening population., Materials and Methods: Women were selected from the UCSF Medical Center screening population that had received both a screening MRI and digital mammogram within one year of each other, had Breast Imaging Reporting and Data System (BI-RADS) assessments of normal or benign finding, and no history of breast cancer or surgery. Agreement was assessed of three mammographic techniques (Single-energy X-ray Absorptiometry [SXA], Quantra, and Volpara) with MRI for percent fibroglandular tissue volume, absolute fibroglandular tissue volume, and total breast volume., Results: Among 99 women, the automated mammographic density techniques were correlated with MRI measures with R(2) values ranging from 0.40 (log fibroglandular volume) to 0.91 (total breast volume). Substantial agreement measured by kappa statistic was found between all percent fibroglandular tissue measures (0.72 to 0.63), but only moderate agreement for log fibroglandular volumes. The kappa statistics for all percent density measures were highest in the comparisons of the SXA and MRI results. The largest error source between MRI and the mammography techniques was found to be differences in measures of total breast volume., Conclusion: Automated volumetric fibroglandular tissue measures from screening digital mammograms were in substantial agreement with MRI and if associated with breast cancer could be used in clinical practice to enhance risk assessment and prevention.

Purpose: To present a novel technique for measuring tissue enhancement in breast fibroglandular tissue regions on contrast-enhanced breast magnetic resonance imaging (MRI) aimed at quantifying the enhancement of breast parenchyma, also known as "background enhancement.", Materials and Methods: Our quantitative method for measuring breast MRI background enhancement was evaluated in a population of 16 healthy volunteers. We also demonstrate the use of our new technique in the case study of one subject classified as high risk for developing breast cancer who underwent 3 months of tamoxifen therapy., Results: We obtained quantitative measures of background enhancement in all cases. The high-risk patient exhibited a 37% mean reduction in background enhancement with treatment., Conclusion: Our quantitative method is a robust and promising tool that may allow investigators to quantify and document the potential adverse effect of background enhancement on diagnostic accuracy in larger populations., (Copyright © 2011 Wiley-Liss, Inc.)

In animal and laboratory models, cancer-associated stroma, or elements of the supporting tissue surrounding a primary tumor, has been shown to be necessary for tumor evolution and progression. However, little is understood or studied regarding the properties of intact stroma in human cancer in vivo. In addition, for breast cancer patients, the optimal volume of local tissue to treat surrounding a primary tumor is not clear. Here, we performed an interdisciplinary study of normal-appearing breast tissue using breast magnetic resonance imaging (MRI), correlative histology and array comparative genomic hybridization to identify a cancer-associated stroma in humans. Using a novel technique for segmenting breast fibroglandular tissue, quantifiable topographic percent enhancement mapping of the stroma surrounding invasive breast cancer was found to be significantly elevated within 2 cm of the tumor edge. This region was also found to harbor increased microvessel density, and genomic changes that were closely associated with host normal breast tissue. These findings indicate that a cancer-associated stroma may be identified and characterized in human breast cancer using non-invasive imaging techniques. Identification of a cancer-associated stroma may be further developed to help guide local therapy to reduce recurrence and morbidity in breast cancer patients.

Recently, 3-T magnetic resonance imaging (MRI) has been introduced for bone imaging. Through higher signal-to-noise ratios, as compared to 1.5-T MRI, it promises to be a more powerful tool for the assessment of cortical and trabecular bone measures. The goal of our study was to compare MRI-derived cortical and trabecular bone measures to quantitative computed tomography (QCT)-derived bone mineral density (BMD). Using 3-T MRI in 51 postmenopausal women, apparent (app.) measures of bone volume/total volume, trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation were derived at the distal radius, distal tibia and calcaneus. Cortical thickness (Ct.Th) was calculated at the distal radius and distal tibia. These measures were compared to QCT-derived BMD of the spine, hip and radius. Significant correlations ((*)P<.05; (**)P<.001; (***)P<.0001) were found between spine BMD- and MRI-derived Ct.Th (r(radius)=.55, (*)P<.05; r(tibia)=.67, (***)P<.0001) and app. Tb.N (r(radius)=.33, (*)P<.05; r(tibia)=.35, (*)P<.05) at the radius and tibia. Furthermore, within the first 10 mm at the radius, an inverse correlation for Ct.Th and app. BV/TV (r(6mm)=-.56, P<.001; r(10mm)=-.36, P<.05) and app. Tb.Th (r(6mm)=-.54, P<.001; r(10mm)=-.41, P<.05) was found., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Diffusion tensor imaging (DTI) of the lumbar spine could improve diagnostic specificity. The purpose of this work was to determine the feasibility of and to validate DTI with single-shot fast spin-echo (SSFSE) for lumbar intervertebral discs at 1.5 and 3 T. Six normal volunteers were scanned with DTI-SSFSE using an eight- and a three-b-value protocol at 1.5 and 3 T, respectively. Apparent diffusion coefficient (ADC) values were computed and validated based on those obtained at 1.5 T from corresponding diffusion tensor scans using line scan diffusion imaging (LSDI), a technique that has been previously validated for use in the spine. Pearson correlation coefficients for LSDI and DTI-SSFSE ADC values were .88 and .89 for 1.5 and 3 T, respectively, with good quantitative agreement according to the Bland-Altman method. Results indicate that DTI-SSFSE is a candidate as a clinical sequence for obtaining diffusion tensor images of the lumbar intervertebral discs with scan times shorter than 4 min.

Purpose: To investigate in vitro the calcaneal trabecular bone structure in elderly human donors with high spatial resolution magnetic resonance (MR) imaging at 3.0 T and 1.5 T, to quantitatively compare MR measures of bone microarchitecture with those from micro-computed tomography (CT), and to compare the performance of 3.0-T MR imaging with that of 1.5-T MR imaging in differentiating donors with spinal fractures from those without spinal fractures., Materials and Methods: The study was performed in line with institutional and legislative requirements; all donors had dedicated their body for educational and research purposes prior to death. Sagittal MR images of 49 human calcaneus cadaveric specimens were obtained (mean age of donors, 79.5 years +/- 11 [standard deviation]; 26 male donors, 23 female donors). After the spatial coregistering of images acquired at 3.0-T and 1.5-T MR imaging, the signal-to-noise-ratios and structural parameters obtained at each magnetic field strength were compared in corresponding sections. Micro-CT was performed on calcaneus cores obtained from corresponding regions in 40 cadaveric specimens. Vertebral deformities of the thoracic and lumbar spine were radiographically classified by using the spinal fracture index. Diagnostic performance of the structural parameters in differentiating donors with vertebral fractures from those without was assessed by using receiver operator characteristic (ROC) analysis, including area under the ROC curve (A(z))., Results: Correlations between structural parameters at 3.0-T MR imaging and those at micro-CT were significantly higher (P < .05) than correlations between structural parameters at 1.5-T MR imaging and those at micro-CT (trabecular thickness, r = 0.76 at 3.0 T vs r = 0.57 at 1.5 T). Trabecular dimensions were amplified at 3.0 T because of increasing susceptibility artifacts. Also, higher ROC values were found for structural parameters at 3.0 T than at 1.5 T, but differences were not significant (trabecular thickness, A(z) = 0.75 at 3.0 T vs A(z) = 0.66 at 1.5 T, P > .05)., Conclusion: MR imaging at 3.0 T provided a better measure of the trabecular bone structure than did MR imaging at 1.5 T. There was a trend for better differentiation of donors with from those without osteoporotic vertebral fractures at 3.0 T than at 1.5 T., ((c) RSNA, 2006.)

Objective: To use receiver operator characteristics (ROC) analysis for assessing the diagnostic performance of three cartilage-specific MR sequences at 1.5 and 3 T in detecting cartilage lesions created in porcine knees., Design: Eighty-four cartilage lesions were created in 27 porcine knee specimens at the patella, the medial and lateral femoral and the medial and lateral tibial cartilage. MR imaging was performed using a fat saturated spoiled gradient echo (SPGR) sequence (in plane spatial resolution/slice thickness: 0.20 x 0.39 mm2/1.5 mm) and two fat saturated proton density weighted (PDw) sequences (low spatial resolution: 0.31 x 0.47 mm2/3 mm and high spatial resolution: 0.20 x 0.26 mm2/2 mm). The images were independently analyzed by three radiologists concerning the absence or presence of lesions using a five-level confidence scale. Significances of the differences for the individual sequences were calculated based on comparisons of areas under ROC curves (A(Z))., Results: The highest A(Z)-values for all three radiologists were consistently obtained for the SPGR (A(Z) = 0.84) and the high-resolution (hr) PDw (A(Z) = 0.79) sequences at 3T. The corresponding A(Z)-values at 1.5 T were 0.77 and 0.69; the differences between 1.5 and 3 T were statistically significant (P < 0.05). A(Z)-values for the low-resolution PDw sequence were lower: 0.59 at 3 T and 0.55 at 1.5 T and the differences between 1.5 and 3T were not significant., Conclusion: With optimized hr MR sequences diagnostic performance in detecting cartilage lesions was improved at 3 T. For a standard, lower spatial resolution PDw sequence no significant differences, however, were found.

Previously, high resolution MRI to assess bone structure of deep-seated regions of the skeleton such as the proximal femur was substantially limited by signal-to-noise ratio (SNR). With the advent of new optimized pulse sequences in MRI at 1.5 T and 3 T, it may now be possible to depict and quantify the trabecular microarchitecture in the proximal femur. The purpose of this study was to investigate the feasibility of assessing trabecular microstructure of the human proximal femur in vivo with MR imaging at 1.5 T and 3 T. MR images of six young, healthy male and female subjects were acquired using standard clinical 1.5-T and high-field 3-T whole-body MR scanners. Using a T2/T1-weighted 3D FIESTA sequence (and a 3D FIESTA-C sequence at 3 T to avoid susceptibility artifacts) a resolution of 0.234 x 0.234 x 1.5 mm(3) was achieved in vivo. Structural parameters analogous to standard bone histomorphometry were determined in femoral head and trochanter regions of interest. Bone mineral density (BMD) measurements were also obtained using dual-energy X-ray absorptiometry (DXA) for the femoral trochanter in the same subjects. The bone structure of the proximal femur is substantially better depicted at 3 T than at 1.5 T. Correlation between the structural parameters obtained at both field strengths was up to R =0.86 for both the femoral head and the trochanteric region. However, the resolution of the images limits the application of 3D structural analysis, making the assessment more akin to 2D textural measures, which may be correlated to histomorphometric but are not identical measures. This feasibility study establishes the potential of MRI as a means of imaging proximal femur structure, and improvements in technique and resolution enhancements are warranted.

Purpose: To compare 1.5- and 3.0-T magnetic resonance (MR) images of porcine knee specimens containing artificial cartilage lesions in terms of accuracy of lesion depiction, image quality, and signal-to-noise ratio (SNR)., Materials and Methods: This Health Insurance Portability and Accountability Act-compliant study had institutional review board approval, and informed consent was obtained from the human volunteers. Two fat-saturated cartilage MR imaging sequences (an intermediate-weighted fast spin-echo [SE] sequence and a spoiled gradient-echo [GRE] sequence) were optimized for imaging at 3.0 T in two human volunteers and then used to image 10 porcine knees in which 29 artificial cartilage lesions had been created. Corresponding sequences were used at 1.5 T for all specimens. Images were assessed by two radiologists in consensus, and diagnostic performance in lesion depiction was determined by using macroscopic findings in specimen slices as a reference standard. SNRs were also calculated. For statistical analysis, the McNemar test of discordant pairs was used with a level of significance of P < .05., Results: The best diagnostic performance for both the intermediate-weighted fast SE and the spoiled GRE sequences was achieved at 3.0 T. With use of corresponding fat-saturated intermediate-weighted fast SE sequences with an identical acquisition time (9 minutes 44 seconds), 26 (90%) of 29 lesions were detected at 3.0 T, while 18 (62%) were detected at 1.5 T. With use of fat-saturated spoiled GRE sequences, 24 (83%) of 29 lesions were detected at 3.0 T (acquisition time, 8 minutes 48 seconds), and 23 (79%) lesions were detected at 1.5 T (acquisition time, 11 minutes 14 seconds). The rate of correct lesion grade assessment was 65% (17 of 26 lesions) at 3.0 T and 61% (11 of 18 lesions) at 1.5 T with the intermediate-weighted fast SE sequences and 83% (20 of 24 lesions) at 3.0 T and 70% (16 of 23 lesions) at 1.5 T with the spoiled GRE sequences. Both subjective evaluation of image quality and SNR values were significantly higher at 3.0 T (P < .05)., Conclusion: In this animal model, MR imaging at 3.0 T increased the accuracy of cartilage lesion assessment when compared with imaging at 1.5 T. Image quality and SNR were highest at 3.0 T., (Copyright RSNA, 2005)

Objective: The purpose of our study was to determine the optimal concentration of a gadolinium-based contrast agent (gadodiamide) for direct MR arthrography at 3 T compared with 1.5 T in an in vitro study., Conclusion: Optimized concentrations of gadolinium-based contrast agents for MR arthrography are similar at 3 and 1.5 T, although a slightly greater dilution may be useful at 3 T. Signal-to-noise ratio peak levels are significantly reduced by adding an iodinated contrast agent, relatively significantly more at 3 T than at 1.5 T.

The purpose of this study is to use high-resolution magnetic resonance (MR) imaging at 3 Tesla (3T) to quantify trabecular bone structure in vitro using femoral head specimens, and to correlate the calculated structure measures with those that were determined using microcomputed tomography (microCT), the standard of reference. Fifteen cylindrical cores were obtained from fresh femoral heads after total hip arthroplasty. MR images were obtained at 3T using a transmit-receive wrist coil. High-resolution coronal images were acquired using a modified three-dimensional (3D) fast-gradient echo sequence. From these data sets two-dimensional (2D) structural parameters analogous to bone histomorphometry were derived by using both mean intercept length (MIL) methods based on the plate model and the more recent model-assumption free 3D distance-transformation (DT) methods. The parameters measured by the 2D plate model-based MIL method and the DT method included apparent (App). BV/TV (bone volume/total volume), App. Tb.Th (trabecular thickness), App. Tb.Sp (trabecular separation), and App. Tb.N (trabecular number). Identical regions of interest were analyzed in the MR images and the microCT data sets, and similar structure measures were derived. The means and standard deviations of the parameters over all slices were calculated and MR-derived measures were correlated with those derived from the microCT data sets using linear regression analyses. Structure measures were overestimated with MRI, for example, the mean App. BV/TV was 0.45 for MRI and 0.20 for microT, and the slope of the graph was 1.45. App. Tb.Th was overestimated by a factor of 1.9, whereas App. Tb.Sp was underestimated; Tb.N showed the smallest effect. Correlations between the individual parameters were excellent (App. BV/TV, r2 = 0.82; App. Tb.Sp, r2 = 0.84; App. Tb.N, r2 = 0.81), except for App.Tb.Th (r2 = 0.67). The results of this study show that trabecular bone structure measures may be obtained using 3T MR imaging. These measures, although higher than the standard of reference, show a highly significant correlation with true structure measures obtained by microCT.

Osteoarthritis (OA) is a disease of articular cartilage degeneration. Early detection of changes in cartilage would be essential for preventing the progression of disease and for monitoring therapy in OA. The T/sub 1rho/ relaxation parameter describes the spin-lattice relaxation in the rotating frame and has been considered as a promising tool to detect the loss of proteoglycan (PG), which is an early precursor of OA. The goal of this study was to develop a T/sub 1rho/-weighted imaging method based on spiral imaging and to examine the feasibility of applying it to in vivo cartilage imaging. T/sub 1rho/-weighted imaging with a pre-encoded spin-lock pulse cluster followed by a spiral acquisition sequence was implemented on GE 1.5 T scanners. tip maps were generated by a pixel-by-pixel fit of the T/sub 1rho/-weighted data to an exponential decay. Homogeneous agarose phantoms and the patella cartilage of one healthy volunteer were imaged using the developed techniques. T/sub 1rho/ in agarose phantoms decreased as agarose concentration increased. No significant tip dispersion was seen within spin-lock frequencies ranging from 150 Hz to 1000 Hz in agarose phantoms. T/sub 1rho/-weighted images of the healthy volunteer showed good contrast between cartilage and surrounding tissues. The fitted T/sub 1rho/ value of patella cartilage was within the range of 30-100 ms.

Rationale and Objectives: A novel, nonlinear morphologic measure [DeltaP(alpha)] based on local 3D scaling properties was applied to high-resolution magnetic resonance images (HR-MRI) of human trabecular bone to predict biomechanical strength in vitro., Methods: We extracted DeltaP(alpha) and traditional morphologic parameters (apparent trabecular volume fraction, apparent trabecular separation) from HR-MR images of 32 femoral and 13 spinal bone specimens. Furthermore, bone mineral density (BMD) and maximum compressive strength (MCS) were determined. The morphologic measures were compared with BMD in predicting the biomechanical strength., Results: In the vertebral (femoral) specimens, R2 for MCS versus DeltaP(alpha) was 0.87 (0.61) (P < 0.001). Correlation between BMD and MCS was 0.53 (P = 0.05) (0.79 [P < 0.001]) for the vertebral (femoral) specimens. For the femoral specimens, prediction of MCS could be improved further by combining BMD and morphologic parameters by multiple regression (R2 = 0.88)., Conclusions: Morphologic measures extracted from HR-MRI considering local 3D-scaling properties can be used to predict biomechanical properties of bone in vitro. They are superior to 2-dimensional standard linear morphometric measures and, depending on the anatomic location, more reliably predict bone strength as measured by MCS than does BMD.

The purpose of this study was to compare trabecular bone structure parameters obtained from high-resolution magnetic resonance (HRMR) and multislice computed tomography (MSCT) images with those determined in contact radiographs from corresponding specimen sections. High-resolution MR and MSCT images were obtained in 39 distal radius specimens. For HRMR the in-plane spatial resolution was 0.152x0.153 mm(2) with a slice thickness of 0.9 and 0.3 mm using a 3D T1-weighted spin-echo sequence. For MSCT the resolution was 0.247x0.247 mm(2) with a collimation of 1 mm. Using a diamond saw, 117 0.9- to 1-mm-thick sections were obtained from these specimens and contact radiographs were acquired. In the corresponding sections structure parameters analogous to bone histomorphometry were determined. Significant correlations between MR- and CT-derived structure parameters and those derived from the contact radiographs were found (p<0.01); r values of up to 0.75 were obtained for HRMR imaging and up to 0.70 for MSCT. On the average, structure parameters showed higher correlations for the MR- than for the CT-derived data. For the MR data the threshold algorithm used for binarizing the images substantially affected these correlations. In conclusion, trabecular bone structure parameters assessed in distal radius HRMR and MSCT images are significantly correlated with those determined in corresponding specimen sections (p<0.01). High-resolution MR-derived structure parameters, however, performed better in the prediction of trabecular bone structure.

The purpose of this study was to use high resolution magnetic resonance imaging (HR-MRI) combined with structure analysis to investigate the trabecular structure of the human proximal femur and to compare this technique with bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) in the prediction of bone strength in vitro. Thirty-one fresh human proximal femur specimens were examined with HR-MRI using a T1-weighted 3D spinecho-sequence in a coronal plane (voxel size: 0.195 x 0.195 x 0.9 mm and 0.195 x 0.195 x 0.3 mm). In these images structure parameters analogous to standard bone histomorphometry were obtained in a femoral head, neck, and trochanteric region of interest (ROI). In addition, BMD measurements were obtained using DXA and finally, all specimens were tested biomechanically in a materials testing machine, and maximum compressive strength (MCS) was determined. Correlations between BMD and MCS were significant (p <0.01) with R-values up to 0.74. Correlating structure parameters and MCS R-values up to 0.69 (P <0.01) were obtained. Using multivariate regression analysis, combining structure parameters and BMD, improved correlations versus MCS substantially (up to R = 0.93; P <0.01). In conclusion, this study showed that in an experimental setting, structure parameters determined in high resolution MR images of the proximal femur correlated significantly with bone strength. The highest correlations, however, were obtained combining BMD and structure measures.

Rationale and Objectives: The authors performed this study to investigate structural variations in the trabecular bone of the proximal femur at high-resolution magnetic resonance (MR) imaging and high-resolution multisection computed tomography (CT)., Materials and Methods: Bone mineral density (BMD) was measured in 36 proximal human femur specimens by using dual x-ray absorptiometry. High-resolution MR imaging was performed at 1.5 T with an in-plane spatial resolution of 0.195 x 0.195 mm and a section thickness of 0.3 and 0.9 mm. Multisection CT was performed with an ultra-high-resolution protocol; images were obtained with an in-plane spatial resolution of 0.25 mm and a section thickness of 1 mm. In a subset of these specimens, micro CT was performed with an isotropic spatial resolution of 30 microm. Identical regions of interest (ROIs) were used to analyze images obtained with MR imaging, multisection CT, and micro CT. Trabecular bone structural parameters were obtained, and the parameters from the individual imaging modalities and BMD were correlated., Results: Significant differences concerning the trabecular microarchitecture between the individual ROIs were demonstrated with multisection CT and MR imaging. A number of the correlations between structural parameters derived with multisection CT, MR imaging, micro CT, and BMD measurements were significant. For MR imaging, threshold technique and section thickness had an effect on structural parameters., Conclusion: Structural parameters obtained in the proximal femur with multisection CT and high-resolution MR imaging show regional differences. These techniques may be useful for depicting the trabecular architecture in the diagnosis of osteoporosis.

An accurate measurement of the transverse relaxation time T(2), and the histogram of T(2) in the brain parenchyma can be accomplished in vivo using a multi-echo magnetic resonance imaging sequence. An estimate of the error in the T(2) measurement is derived using copper sulfate doped water phantoms. Correction factors are calculated and applied to the signal intensity of each voxel prior to the in vivo T(2) evaluation. These corrected T(2) are in good agreement with the theoretical values calculated from copper sulfate concentrations. This technique is then applied to calculate T(2) histograms of the brain. The population studied was composed of normal volunteers and multiple sclerosis patients. The corrected T(2) histogram method discriminates the normal control population from the MS population, and also discriminates between relapsing-remitting patients and primary progressive or secondary progressive patients. Moreover using this approach we are able to detect in MS patients a global shift of the T(2) of the white mater toward higher values. The results of this study showed that the method is easy to implement and may be used to characterize MS pathology.

Previous studies indicate that Multiple Sclerosis (MS) patients exhibit deficits in tests of explicit memory such as free recall, but show normal priming on implicit tests of memory such as word stem completion. However, the memory performance of patients with different MS disease subtypes has not been fully examined. In the current study, memory was assessed in Primary Progressive (PPMS), Relapsing Remitting (RRMS), and Secondary Progressive (SPMS) MS subgroups. Explicit memory as well as perceptual and conceptual implicit memory were examined using free recall, word fragment completion, and exemplar generation tests, respectively. All three groups of MS patients exhibited free recall deficits and normal priming on the exemplar generation test. However, the PPMS group exhibited a deficit in word fragment completion priming, whereas the RRMS and SPMS groups exhibited normal levels of priming on this task. Lesion load was assessed using magnetic resonance imaging and was negatively correlated with explicit memory performance, but it did not account for the observed deficits in perceptual implicit memory. The results indicate that PPMS patients exhibit a pattern of memory impairment that is distinct from that of the RRMS and SPMS groups. Moreover, the results indicate that perceptual implicit memory can be neurologically dissociated from conceptual implicit memory.

The aim of this study was to compare structure measures obtained from high-resolution MR images of the calcaneus and the distal radius with bone mineral density (BMD) of the spine and hip in the prediction of osteoporotic spine fracture status. High-resolution MR images of the calcaneus and radius were obtained in 24 post-menopausal women with spine fractures and 22 age-matched controls. Imaging was performed at 1.5 T using a T1-weighted spin-echo sequence (slice thickness 1 mm, in-plane spatial resolution 195 x 195 microm(2)). Structure analysis was performed using parameters analogous to standard histomorphometry. Bone mineral density of the spine was obtained using quantitative CT and of the hip with dual-energy X-ray absorptiometry. Significant differences between both patient groups were obtained with BMD and all structure parameters ( p<0.05). Using receiver operating characteristic analysis to determine the diagnostic performance in differentiating both groups, the best results were found for BMD of the spine, one of the radial structure measures and a combination of the calcaneal structure measures. In this study BMD of the spine and structure measures of the distal radius were best suited to predict the osteoporotic fracture status of the spine. A combination of BMD and structure measures did not yield any additional information on fracture status.

Objective: To investigate whether recently developed in vivo high-resolution magnetic resonance-imaging and micro-finite element techniques can monitor changes in bone mechanical properties during long-term clinical trials aiming at evaluating the efficacy of new drugs for the treatment of osteoporosis., Design: Comparison of baseline and follow-up mechanical parameters calculated using micro-finite element analysis of the calcaneus for subjects participating in a study investigating the effect of idoxifene., Background: Contemporary measurements for the evaluation of bone mechanical properties, based on dual-energy X-ray absorptiometry measurements, are not very accurate and require large trial populations., Methods: A total of 56 postmenopausal subjects received either a placebo, 5 mg or 10 mg per day of idoxifene. Magnetic resonance-images of the calcaneus were made at baseline and after one year. Mechanical parameters of a trabecular volume of interest in the calcaneus were calculated using micro-finite element analysis., Results: Although there were no significant differences between the mean changes in the treated groups and the placebo group, there were significant changes from baseline within groups after one year of treatment. Significant changes, however, were found only for mechanical parameters and only in the treated groups., Conclusions: The present study is the first demonstration that longitudinal changes in bone mechanical properties due to trabecular micro-architectural changes may be quantified in long-term clinical studies. Since significant changes in mechanical parameters were obtained for the treated groups whereas no significant change in bone mass was found we conclude that the application of these techniques may increase the clinical significance of these trials., Relevance: A precise diagnosis of in vivo bone mechanical properties that accounts for (changes in) trabecular bone architecture is of particular importance for longitudinal clinical trials aiming at evaluating the efficacy of new drugs since it can lead to clinically relevant results from shorter follow-up intervals and may enable a reduction of the number of patients involved in the trial.

Complementing measurements of bone mass with measurements of the architectural status of trabecular bone is expected to improve predictions of fracture risk in osteoporotic patients and improve the assessment of response to drug therapy. With high-resolution MRI the trabecular network can be imaged with 156 x 156 x 500 microm3 voxels, sufficient to depict individual trabeculae, albeit with inaccurate thickness. In this work, distance transformation techniques were applied to the three-dimensional image of the distal radius of postmenopausal patients. Structural indices such as trabecular number (app.Tb.N), thickness (app.Tb.Th) and separation (app.Tb.Sp) were determined without model assumptions. A new metric index, the apparent intra-individual distribution of separations (app.Tb.Sp.SD), is introduced. The reproducibility of the MR procedure and structure assessment was determined on volunteers, and the coefficient of variation was found to be 2.7-4.6% for the mean values of structural indices and 7.7% for app.Tb.Sp.SD. The distance transformation methods were then applied to two groups of patients: one of postmenopausal women without vertebral fracture and one of postmenopausal women with at least one vertebral fracture. It was found that app.Tb.Sp.SD discriminates fracture subjects from non-fracture patients as well as dual-energy X-ray absorptiometry (DXA) measurements of the radius and the spine, but not as well as DXA of the hip. Using receiver operating characteristic analysis, the area under the curve (AUC) values were 0.67 for app.Tb.Sp.SD, 0.72 for DXA radius, 0.67 for DXA spine and 0.81 for DXA of the hip. A combination of MR indices reached an AUC of 0.75. Age-adjusted odds ratio ranged from 1.85 to 2.03 for app.Tb.N, app.Tb.Sp and app.Tb.Sp.SD (p<0.003). We conclude that in vivo high-resolution MRI not only has the potential of imaging trabecular bone, but in combination with novel metrics may offer new insight into the structural changes occurring in postmenopausal women.

The authors have developed a system for the characterization of trabecular bone structure from high-resolution MR images. It features largely automated coil inhomogeneity correction, trabecular bone region segmentation, serial image registration, bone/marrow binarization, and structural calculation steps. The system addresses problems of efficiency and inter- and intraoperator variability inherent in previous analyses. The system is evaluated on repetitive scans of 8 volunteers for both two-dimensional (2D) apparent structure calculations and three-dimensional (3D) mechanical calculations using micro-finite element analysis. Coil correction methods based on a priori knowledge of the coil sensitivity and on low-pass filtering of the high-resolution mages are compared and found to perform similarly. Image alignment is found to cause small but significant changes in some structural parameters. Overall the automated system provides on the order of a 3-fold decrease in trained operator time over previous manual methods. Reproducibility is found to be dependent on image quality for most parameters. For 7 subjects with good image quality, reproducibility of 2-4% is found for 2D structural parameters, while 3D mechanical parameters vary by 4-9%, with percent standardized coefficients of variation in the ranges of 15-34% and 20-38% respectively.

The purpose of this study was to use high-resolution magnetic resonance (HR-MR) imaging to analyze the trabecular bone structure of the calcaneus in patients before and after renal transplantation and to compare this technique with bone mineral density (BMD) in predicting therapy-induced bone loss and osteoporotic fracture status. HR-MR imaging (voxel size: 0.195 x 0.195 x 1 mm) was performed at 1.5 T with an axial and sagittal orientation in 48 patients after transplantation, 12 patients before renal transplantation and 20 healthy controls. Structure measures analogous to standard histomorphometry and fractal dimension were determined in these images. BMD measurements of the lumbar spine and the proximal femur were obtained in the healthy female controls and the patients. Vertebral and peripheral fracture status were determined in all patients. The structural measures app.BV/TV, Tb.Sp, Tb.Th and Tb.N showed significant differences between controls and patients (p<0.05) while fractal dimension showed no significant differences. Neither the structural measures nor BMD showed significant differences between patients before and after transplantation. Correlations between time after transplantation versus structural measures and BMD were not significant. Differences between fracture and nonfracture patients were significant for the structural measures app.BV/TV, Tb.Sp and Tb.N (axial images) as well as for app.Tb.Th (sagittal images) and spine BMD (p<0.05) but not for hip BMD. Using odds ratios the strongest discriminators between patients with and without fractures were app. BV/TV, app.Tb.Sp (axial images) and app.Tb.Th (sagittal images), even after adjustment for age and BMD. Using receiver operating characteristic analysis the highest diagnostic performance was found for a combination of BMD and structural measures. In conclusion, our results indicate that structural measures obtained from HR-MR images may be used to characterize fracture incidence in kidney transplant patients; the best results, however, are obtained using a combination of BMD and structural measures.

Measurement of microstructural parameters of trabecular bone noninvasively in vivo is possible with high-resolution magnetic resonance (MR) imaging. These measurements may prove useful in the determination of bone strength and fracture risk, but must be related to other measures of bone properties. In this study in vivo MR imaging was used to derive trabecular bone structure measures and combined with micro-finite element analysis (microFE) to determine the effects of trabecular bone microarchitecture on bone mechanical properties in the distal radius. The subjects were studied in two groups: (I) postmenopausal women with normal bone mineral density (BMD) (n = 22, mean age 58 +/- 7 years) and (II) postmenopausal women with spine or femur BMD -1 SD to -2.5 SD below young normal (n = 37, mean age 62 +/- 11 years). MR images of the distal radius were obtained at 1.5 T, and measures such as apparent trabecular bone volume fraction (App BV/TV), spacing, number and thickness (App TbSp, TbN, TbTh) were derived in regions of interest extending from the joint line to the radial shaft. The high-resolution images were also used in a micro-finite element model to derive the directional Young's moduli (E1, E2 and E3), shear moduli (G12, G23 and G13) and anisotropy ratios such as E1/E3. BMD at the distal radius, lumbar spine and hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed by serum osteocalcin and bone resorption by serum type I collagen C-terminal telopeptide breakdown products (serum CTX) and urinary CTX biochemical markers. The trabecular architecture displayed considerable anisotropy. Measures of BMD such as the ultradistal radial BMD were lower in the osteopenic group (p<0.01). Biochemical markers between the two groups were comparable in value and showed no significant difference between the two groups. App BV/TV, TbTh and TbN were higher, and App TbSp lower, in the normal group than the osteopenic group. All three directional measures of elastic and shear moduli were lower in the osteopenic group compared with the normal group. Anisotropy of trabecular bone microarchitecture, as measured by the ratios of the mean intercept length (MIL) values (MIL1/MIL3, etc.), and the anisotropy in elastic modulus (E1/E3, etc.), were greater in the osteopenic group compared with the normal group. The correlations between the measures of architecture and moduli are higher than those between elastic moduli and BMD. Stepwise multiple regression analysis showed that while App BV/TV is highly correlated with the mechanical properties, additional structural measures do contribute to the improved prediction of the mechanical measures. This study demonstrates the feasibility and potential of using MR imaging with microFE modeling in vivo in the study of osteoporosis.

Study Design: Twelve lumbar intervertebral disc specimens were imaged with magnetic resonance imaging to estimate relaxation constants, T1 and T2, and tissue water diffusion, before and after applying compression., Objectives: The objectives of the study were to measure T1, T2, and water diffusion for differences with loading state, region of the disc (anulus fibrosus or nucleus pulposus), and grade of degeneration., Summary of Background Data: Magnetic resonance imaging can be used qualitatively to estimate water content and degeneration of the intervertebral disc. Beyond structural information of images, the relaxation times T1 and T2 may contain information on the changes occurring with degeneration. A modified spin-echo sequence can be used to estimate tissue water diffusion in cartilage and disc specimens with the ability to measure anisotropy., Methods: Specimens were imaged in a 1.5-Tesla clinical scanner. T1, T2, and water diffusion were estimated from midsagittal images. Magnetic resonance imaging parameters were calculated before and after axial loading. The measured T1, T2, and D (diffusion coefficient) were compared before and after compression, and for the diffusion data, also by direction to consider anisotropy., Results: For the T1 data, a significant difference was found by region, nucleus > anulus, and loading state, loaded > unloaded. For the T2 values, there was a significant difference by region, nucleus > anulus, and Thompson grade. For diffusion, significant differences were found by region, nucleus > anulus, Thompson grade, direction of diffusion, and state of compression, loaded > unloaded., Conclusions: This study demonstrated that magnetic resonance imaging can be used to measure significant changes in T1, T2, or diffusion in intervertebral disc specimens by region, loading condition, or Thompson grade.

The purpose of this study was to use quantitative magnetic resonance imaging (MRI; high-resolution [HR] and relaxometry) to assess trabecular bone structure in lumbar vertebrae specimens and to compare these techniques with bone mineral density (BMD) in predicting stress values obtained from mechanical tests. Fourteen vertebral midsagittal sections from lumbar vertebrae L3 were obtained from cadavers (aged 22-76 years). HR images with a slice thickness of 300 microm and an in-plane spatial resolution of 117 microm2 x 117 microm2 were obtained. Transverse relaxation time T2' distribution was measured by using an asymmetric spin-echo (ASE) sequence. Traditional morphometric measures of bone structure such as apparent trabecular bone fraction (app. BV/TV), apparent trabecular bone number (app. Tb.N), apparent trabecular bone separation (app. Tb.Sp), and apparent trabecular bone thickness (app. Tb.Th) as well as the directional mean intercept length (MIL) were calculated. Additionally, BMD measurements of these sections were obtained by dual-energy X-ray absorptiometry (DXA) and biomechanical properties such as directional stress values (to fracture) were determined on adjacent specimens. With the exception of T2', all morphological parameters correlated very well with age, BMD, and stress values (R between 0.79 and 0.92). However, in the direction perpendicular to the magnetic field, T2' values enhanced the adjusted R2 correlation value with horizontal (M/L) stress values in addition to BMD from 0.70 to 0.91 (p < 0.05).

Rationale and Objectives: The purpose of this study was to compare trabecular bone structure parameters assessed with high-resolution magnetic resonance imaging (HR-MRI) with those determined in specimen sections., Methods: High-resolution MR images were obtained for 30 calcaneus specimens with a three-dimensional, T1-weighted spin-echo sequence (spatial in-plane resolution 0.195 mm, slice thicknesses of 0.3 and 0.9 mm). Thirty-eight sections were obtained from the specimens, and contact radiography was performed. In the corresponding sections, structural parameters analogous to bone histomorphometry were determined., Results: Significant correlations between MRI-derived structural parameters and those derived from macro pathological sections were found: r values of up to 0.75 were obtained (P < 0.01). The highest correlations were found for apparent bone volume/total volume and trabecular thickness. Image thresholding techniques showed a significant impact on these correlations (P < 0.01). The thinner MR sections were less susceptible to the different thresholding algorithms., Conclusions: Trabecular bone structure depicted by HR-MR images is significantly correlated with that shown in macro sections (P < 0.01); however, a number of limitations have to be considered, including the substantial impact of thresholding techniques and slice thickness.

Purpose: To use high-spatial-resolution magnetic resonance (MR) imaging to analyze the trabecular bone structure of the calcaneus in patients before and after heart transplantation and to compare this technique with bone mineral density (BMD) measurement in predicting therapy-induced bone loss and vertebral fracture status., Materials and Methods: High-spatial-resolution 1.5-T MR imaging of the calcaneus was performed in 40 men 11-120 months after heart transplantation, in 11 men before heart transplantation, and in 10 age-matched male volunteers. Sagittal and transverse T1-weighted spin-echo images with a voxel size of 0.195 x 0.195 x 1.000 mm were obtained, and structure measurements analogous to bone histomorphometric values were calculated. In addition, the BMD of the lumbar spine was determined in the transplant recipients pre- and postoperatively by using quantitative computed tomography, and vertebral fracture status was assessed., Results: Significant differences in structure and BMD measurements were found between patients before and after heart transplantation (P <. 05). In 17 (42%) of 40 transplant recipients, vertebral fractures were found. Although structure measurements were significantly different between patients with and those without fractures (P <.05), BMDs were not. Correlations between time after transplantation and some structure measurements were moderately significant (P <. 05), but such correlations with BMD measurements were not., Conclusion: MR imaging-derived structure measurements in the calcaneus are useful for monitoring bone changes after heart transplantation and assessing vertebral fracture status.

Our purpose in this study was (i) to measure trabecular bone structure using fractal analysis of distal radius radiographs in subjects with and without osteoporotic hip fractures, and (ii) to compare these measures with bone mineral density (BMD) as well as with measures of trabecular bone structure derived from high resolution magnetic resonance (MR) images. Distal radius radiographs were obtained using semi-industrial films (55 kVp, 400 mAs) in 30 postmenopausal patients, who had suffered osteoporotic hip fractures (74.8+/-8.2 years) in the last 24 months and 27 postmenopausal age-matched (74.6+/-6.6 yr) normal volunteers. Radiographs were digitized at 50 microm. A Fourier power spectrum-based fractal dimension (FD) characterizing the trabecular pattern was measured in a region of interest proximal to the joint line. The fractal dimension was calculated over two spatial frequency (f) ranges: FD1 was calculated over 0.5

This cross-sectional study is based on images from the lower leg as assessed by peripheral quantitative computer tomography (pQCT). Measurements were performed in 39 female and 38 male control subjects and 15 female professional volleyball players, all between 18 and 30 years of age. The images were obtained at shank levels of 4%, 14%, 33%, and 66% from the distal end. Bone and muscle cross-sectional areas, and the bones' density-weighted area moment of resistance and of inertia were assessed. From these, muscle-bone strength indices (MBSIs) were developed for compression (CI = 100. bone area/muscle area) and bending (BI = 100. bone area moment of resistance/muscle area/tibia length). Significant correlations between muscle cross-sectional area and bone were found at all section levels investigated. The strongest correlation for compression was observed in the sections at 14% (correlation coefficient r = 0.74), where 4.10 +/- 0.46 cm(2) bone, on average, was related to 100 cm(2) muscle. The compression index (CI) at the 14% level was independent of the tibia length. Interestingly, the 15 athletes had significantly greater CIs than the control subjects. This is most probably due to the greater tension development in the athletes. The highest correlation for bending was for anteroposterior bending at 33% of tibia length (r = 0.81), where the area moment of resistance, R, was on, average, 4.21 +/- 0.54 cm(3)/100 cm(2) muscle/m tibia length. Analysis of the bones' area moment of inertia showed that buckling is a possible cause of bending at the 33% and 66% levels, but not at the 14% level. No gender differences in MBSI were found. Likewise, age was without significant effect. The data show that bone architecture depends critically on muscle cross section and tension development. Moreover, bone geometry (e.g., the tibia length) influences the geometrical distribution of bone mineral, as it was found that long bones adapted to the same compressive strength are wider than short ones. We conclude that MBSIs offer a powerful diagnostic tool for bone disorders and may contribute to improving the treatment of bone metabolic and other diseases.

A three-dimensional technique was developed for the quantification of the number and cross-sectional geometry of individual trabeculae oriented along a given direction. As an example application, the number of vertical and horizontal trabeculae and their respective cross-sectional geometry were determined for a set of six vertebral cancellous bone specimens (L3-L4 female vertebral bodies; age range 39-63 years). Three-dimensional optical images at a spatial resolution of 20 microm were obtained using an automated serial milling technique. The thickness distributions were generally right skewed. The mean true thickness for both the vertically and horizontally oriented trabeculae showed a strong relationship with volume fraction (vertical: r2 = 0.86; p < 0.05; horizontal: r2 = 0.80; p < 0.05), and mean trabecular thickness (Tb.Th.) (vertical: r2 = 0.81; p < 0.05; horizontal: r2 = 0.72; p < 0.05). The horizontal trabeculae were greater in number and were thinner than the vertical trabeculae. The coefficient of variation of the intraspecimen vertical trabecular thicknesses ranged from 25% to 42%, and showed a weak, albeit insignificant, positive correlation with volume fraction (r2 = 0.46). The findings demonstrated substantial intraspecimen variations exist in trabecular thickness that are not related to volume fraction. Further studies are recommended to determine the potential role of such intraspecimen variations in architecture on biomechanical properties.

The purpose of this study was to determine whether fractal dimension of radiographs provide measures of trabecular bone structure which correlate with bone mineral density (BMD) and bone biomechanics, and whether these relationships depend on the technique used to calculate the fractal dimension. Eighty seven cubic specimen of human trabecular bone were obtained from the vertebrae and femur. The cubes were radiographed along all three orientations--superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP), digitized, corrected for background variations, and fractal based techniques were applied to quantify trabecular structure. Three different techniques namely, semivariance, surface area, and power spectral methods were used. The specimens were tested in compression along three orientations and the Young's modulus (YM) was determined. Compressive strength was measured along the SI direction. Quantitative computed tomography was used to measure trabecular BMD. High-resolution magnetic-resonance images were used to obtain three-dimensional measures of trabecular architecture such as the apparent bone volume fraction, trabecular thickness, spacing, and number. The measures of trabecular structure computed in the different directions showed significant differences (p<0.05). The correlation between BMD, YM, strength, and the fractal dimension were direction and technique dependent. The trends of variation of the fractal dimension with BMD and biomechanical properties also depended on the technique and the range of resolutions over which the data was analyzed. The fractal dimension showed varying trends with bone mineral density changes, and these trends also depended on the range of frequencies over which the fractal dimension was measured. For example, using the power spectral method the fractal dimension increased with BMD when computed over a lower range of spatial frequencies and decreased for higher ranges. However, for the surface area technique the fractal dimension increased with increasing BMD. Fractal measures showed better correlation with trabecular spacing and number, compared to trabecular thickness. In a multivariate regression model inclusion of some of the fractal measures in addition to BMD improved the prediction of strength and elastic modulus. Thus, fractal based texture analysis of radiographs are technique dependent, but may be used to quantify trabecular structure and have a potentially valuable impact in the study of osteoporosis.

To determine whether magnetic resonance (MR)-derived measures of trabecular bone architecture in the distal radius are predictive for prevalent hip fractures, 20 subjects with hip fractures and 19 age-matched postmenopausal controls were studied. Bone mineral density (BMD) measures at the hip (dual-energy X-ray absorptiometry, DXA) and the distal radius (peripheral quantitative computed tomography, pQCT) were also obtained. We compared the MR-based structural measures derived in the radius with those in the calcaneus of the same patients. In the radius, images were acquired at an in-plane resolution of 156 microm and a slice thickness of 0.5 mm. Stereologic measures such as the apparent trabecular thickness (app. Tb.Th), fractional trabecular bone volume (app. BV/TV), trabecular spacing (app. Tb.Sp) and trabecular number (app. Tb.N) were derived from the images. Measures of app. Tb.Sp and app. Tb.N in the distal radius showed significant (p<0.05) differences between the two groups, as did hip BMD measures. However, radial trabecular BMD measures showed only a marginal difference (p = 0.05). Receiver operating curve analysis was used to determine the diagnostic efficacy of BMD, structural measures and a combination of the two. The area under the curve (AUC) for total hip BMD was 0.73, and for radial trabecular BMD was 0.69. AUC for most of the measures of trabecular bone structure at the distal radius was lower than for hip BMD measures; however, AUC for app. Tb.N at the radius was 0.69, comparable to trabecular BMD using pQCT. The AUC for combined BMD (hip) and structure measures was higher (0.87) when radius and calcaneus structure was included. Measures of trabecular architecture derived from MR images combined with BMD measures improve the discrimination between subjects with hip fractures and normal age-matched controls.

Studies have indicated that quantitative ultrasound (QUS) variables may be influenced by the mechanical properties of bone which in turn are determined by bone's material and structural properties. However, from these studies it is unclear what role density, elasticity, and structure play in determining velocity. Eighteen defatted, 12-mm cubic trabecular bone specimens were cut from cadaveric specimens. Amplitude-dependent speed of sound (SOS) using a single point QUS system was assessed in three orthogonal axes. Magnetic resonance images were obtained, from which measures of apparent trabeuclar structure were derived. The specimens were nondestructively tested in compression along three orthogonal axes defined by the sides of the cubes. The elastic modulus (in the three directions) and the strength (in one direction) were determined. Trabecular BMD was measured by quantitative computed tomography. SOS varied significantly with direction of measurement, with the highest value in the axial direction (axial:1715 m/s, sagittal: 1662 m/second, and coronal: 1676 m/s). SOS of each of the three axes was generally associated with the various mechanical (r = 0.30-0.87), density (r = 0.81-0.93), and bone structural variables (0.3-0.8). However, after adjusting the SOS correlations by density, only the correlation with elasticity remained significant in the coronal direction. BMD alone explained 88-93% of variance in SOS whereas in the multivariate model, BMD plus elasticity and/or anisotropic variables explained 96-98% of the variance in SOS. Variability of SOS is explained mostly by density and to a small extent by elasticity or anisotropy. Since only 2-6% of the variance of the QUS measurement is not explained by density and elasticity, one could conclude that the remaining variance reflects other properties of bone or perhaps simply measurement error. Evidence that these other properties may be structure related is only found in the anisotropy of QUS parameter.

Conventional radiography and fractal analysis were used to quantify trabecular texture patterns in human femur specimens and these measures were used in conjunction with bone mineral density (BMD) to predict bone strength. Radiographs were obtained from 51 human femur specimens (25 male, 26 female). The radiographs were analyzed using three different fractal geometry based techniques, namely semi-variance, surface area and Fourier analysis. Maximum compressive strength (MCS) and shear stress (MSS) were determined with a material testing machine: BMD was measured using quantitative computed tomography (QCT). MCS and MSS both correlated significantly with BMD (MCS: R = 0.49-0.54; MSS: R = 0.69-0.72). Fractal dimension also correlated significantly with both biomechanical properties (MCS: R = 0.49-0.56; MSS: R = 0.47-0.54). Using multivariate regression analysis, the fractal dimension in addition to BMD improved correlations versus biomechanical properties. Both BMD and fractal dimension showed statistically significant correlation with bone strength. The fractal dimension provided additional information beyond BMD in correlating with biomechanical properties.

Trabecular bone structure and bone density contribute to the strength of bone and are potentially important in the study of osteoporosis. Fourier transforms of the textural patterns in radiographs of trabecular bone have previously been used for the measurement of trabecular bone structure in subjects, however, the relationship between these measures and biomechanical properties of bone have not previously been established. In this study radiographs were acquired of 28 cubic specimens of spinal trabecular bone along each of the three anatomic axes: cranio-caudal or superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP). The radiographs were digitized, background corrected, and uniformly aligned. The Fast Fourier transform (FFT) was performed on a region comprised solely of trabecular bone for each image. The zero (DC), first (FMO), and second moments (SMO) of the Fourier power spectrum and the fractal dimension (FD) as determined from the Fourier power spectrum were correlated with stereology measures, with bone mineral density (BMD) as well as with measured biomechanical properties [Young's elastic modulus (YM) and ultimate strength] of the cubes. The results show that the power spectra-based measures, when compared with structural parameters determined using 3D stereology, show good correlations with bone volume fraction, trabecular spacing, thickness, and number. These power spectral measures showed fair to good correlations with BMD and the biomechanical properties. Moreover, the correlations between the power spectral measures of trabecular structure and the BMD, YM, and stereology measures of structure depend on the orientation of the radiographic image. Specifically, these were significant differences in the measured biomechanical properties and the power spectral measures of the trabecular structure between the SI and ML and the SI and AP directions. In addition, depending on the spatial frequency range for analysis, the fractal dimension showed opposite trends with changes in BMD and biomechanical properties. Multivariate regression models showed the correlation coefficients increasing with the inclusion of some of the power spectral measures, suggesting that FFT-based texture analysis may play a potential role in studies of osteoporosis.

Recently, new micro-finite element (micro-FE) techniques have been introduced to calculate cancellous bone mechanical properties directly from high-resolution images of its internal architecture. Also recently, new peripheral quantitative computed tomography (pQCT) and magnetic resonance (MR) imaging techniques have been developed that can create images of whole bones in vivo with enough detail to visualize the internal cancellous bone architecture. In this study we aim to investigate if the calculation of cancellous bone mechanical properties from micro-FE models based on such new pQCT and MR images is feasible. Three bone specimens were imaged with the pQCT scanning system and the MR-imaging system. The specimens were scanned a second time using a micro-CT scanner with a much higher resolution. Digitized reconstructions were made based on each set of images and converted to micro-FE models from which the bone elastic properties were calculated. It was found that the results of both the pQCT and the MR-based FE-models compared well to those of the more accurate micro-CT based models in a qualitative sense, but correction factors will be needed to get accurate values.

Purpose: To use T2* measurements at magnetic resonance (MR) imaging to investigate the trabecular structure of the hip in women with and women without osteoporotic hip fractures and to compare this technique with bone mineral density (BMD) measurements in the diagnosis of fractures., Materials and Methods: T2* maps of the proximal femur were obtained at 1.5 T in 23 postmenopausal study patients with osteoporotic hip fractures, 27 age-matched healthy postmenopausal control subjects, and five healthy premenopausal control subjects. A modified gradient-recalled acquisition in the steady state, or GRASS, sequence was used with echo times of 4-40 msec at 4-msec increments. T2* values were measured in five regions of interest: femoral neck, the Ward triangle, trochanter, intertrochanteric region, and total proximal femur. Additionally, BMD measurements of the hip were obtained with dual x-ray absorptiometry., Results: Significant differences between T2* measurements were obtained in all three groups (P < .05). BMD measurements of the hip also showed significant differences (P < .05). For T2* and BMD measurements, odds ratios and areas under the curve in receiver operating characteristic analysis were comparable. Correlations between 1/T2* values and BMD were significant (P < .05). T2* measurements in the proximal femur showed regional variations., Conclusion: MR imaging decay characteristics of bone marrow could be used to differentiate between postmenopausal women with and those without osteoporotic hip fractures.

The measurement of bone microstructure as well as bone mineral density may improve the estimation of bone strength. Cubic specimens (N = 26, 12 mm X 12 mm X 12 mm) of human cadaver vertebrae were cut along three orthogonal anatomic orientations, i.e., superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP). Contact radiographs of the bone cubes along all three orientations were obtained and then digitized by a laser scanner with pixel size of 50 microns x 50 microns. The specimens were tested in compression along the 3 orthogonal orientations and the Young's modulus (YM) was calculated for each direction. Quantitative computed tomography (QCT) was used to obtain a measure of trabecular bone mineral density (BMD). Global gray level thresholding and local thresholding algorithms were used to extract the trabecular bone network. Apparent trabecular bone fraction (ABV/TV), mean intercept length (I.TH), mean intercept separation (I.SP), and number of nodes (N.ND) were measured from the extracted trabecular network. Fractal dimension (Fr.D) of the trabecular bone texture was also measured. Paired t-tests showed that the mean values of each texture parameter (except ABV/TV) and of YM along the SI direction were significantly different (p < 0.05) from those along the ML and AP direction. However, the mean values along the ML and AP directions were not significantly different. Multivariate regression of YM as a function of the texture parameters and BMD showed that without adjusting for the effect of BMD, YM was significantly explained by all the texture parameters (R2 = 0.2-0.6). When BMD was included in the regression, although the variations in YM of ML, AP, and SI orientations could be explained by BMD alone, some of the texture parameters did improve the overall prediction of the biomechanical properties, while, some parameters such as ABV/TV and Fr.D in the ML orientation showed a more significant overall effect in explaining mechanical strength than did BMD. In conclusion, trabecular texture parameters correlated significantly with BMD and YM. Trabecular texture parameters from projectional radiographs reflect the anisotropy of trabecular structure. Quantitative radiographic assessment of trabecular structure using fine-detail radiography can potentially improve the estimation of bone strength.

Osteoporosis is characterized by reduced bone mass and a deterioration of bone structure which results in an increased fracture risk. The purpose of this review is to evaluate structure analysis techniques in the diagnosis of osteoporosis. Several imaging techniques were applied to analyze trabecular bone, such as conventional radiography, high-resolution computed tomography (HR-CT) and high-resolution magnetic resonance imaging (HR-MRI). The best results were obtained using high-resolution tomographic techniques. The highest spatial resolutions in vivo were achieved using HR-MRI. These studies show that texture parameters and bone mineral density predict bone strength and osteoporotic fractures in a complementary fashion. Combining both techniques yields the best results in the diagnosis of osteoporosis.

The purpose of this study was to use high resolution (HR) magnetic resonance (MR) images of the calcaneus to investigate the trabecular structure of patients with and without osteoporotic hip fractures and to compare these techniques with bone mineral density (BMD) in differentiating fracture and nonfracture patients. Axial and sagittal HR MR images of the calcaneus were obtained in 50 female (23 postmenopausal patients with osteoporotic hip fractures and 27 postmenopausal controls). A three-dimensional gradient-echo sequence was used with a slice thickness of 500 micron and in plane resolution of 195 x 195 micron. Texture analysis was performed using morphological features, analogous to standard histomorphometry and fractal dimension. Additionally, BMd measurements of the hip (dual-energy X-ray absorptiometry) were obtained in all patients. Significant differences between both patient groups were obtained using morphological parameters and fractal dimension as well as hip BMD (p < 0.05). Odds ratios for the texture parameters apparent (app.) bone volume/total volume and app. trabecular separation were higher than for hip BMD. Receiver operator characteristic values of texture measures and hip BMD were comparable. In conclusion, trabecular structure measures derived from HR MR images of the calcaneus can differentiate between postmenopausal women with and without osteoporotic hip fractures.