MRI measurement of bone marrow cellularity for radiation dosimetry.

UNLABELLED: The current gold standard for measuring marrow cellularity is the bone marrow (BM) biopsy of the iliac crest. This measure is not predictive of total marrow cellularity, because the biopsy volume is typically small and fat fraction varies across the skeleton. MRI and localized MR spectroscopy have been demonstrated as noninvasive means for measuring BM cellularity in patients. The accuracy of these methods has been well established in phantom studies and in the determination of in vivo hepatic fat fractions but not for in vivo measurement of BM cellularity. METHODS: Spoiled gradient-echo in vivo images of the femur, humerus, upper spine, and lower spine were acquired for 2 dogs using a clinical 3-T MRI scanner. Single-peak iterative decomposition of water and fat with echo asymmetry and least squares (SP-IDEAL) was used to derive BM fat fractions. Stimulated-echo acquisition mode spectra were acquired in order to perform multipeak IDEAL with precalibration (MP-IDEAL). In vivo accuracy was validated by comparison with histology measurements. Histologic fat fractions were derived from adipocyte segmentation. RESULTS: Bland-Altman plots demonstrated excellent agreement between SP-IDEAL and histology, with a mean difference of -0.52% cellularity and most differences within ±2% cellularity, but agreement between MP-IDEAL and histology was not as good (mean difference, -7% cellularity, and differences between 5% and -20%). CONCLUSION: Adipocyte segmentation of histology slides provides a measure of volumetric fat fraction (i.e., adipocyte volume fraction [AVF]) and not chemical fat fraction, because fat fraction measured from histology is invariant to the relative abundances of lipid chemical species. In contrast, MP-IDEAL provides a measure of chemical fat fraction, thus explaining the poor agreement of this method with histology. SP-IDEAL measures the relative abundance of methylene lipids, and this measure is shown to be equivalent to AVF. AVF provides the appropriate parameter to account for patient-specific cellularity in BM mass predictive equations and is consistent with current micro-CT-based models of skeletal dosimetry.

Method for estimating skeletal spongiosa volume and active marrow mass in the adult male and adult female.

UNLABELLED: Active bone marrow is one of the more radiosensitive tissues in the human body and, hence, it is important to predict and possibly avoid myelotoxicity in radionuclide therapies. The MIRD schema currently used to calculate marrow dose generally requires knowledge of the patient's total skeletal active marrow mass -- a value that, at present, cannot be directly measured. Conceptually, the active marrow mass in a given skeletal region may be obtained given knowledge of the trabecular spongiosa volume (SV) of the bone site. A recent study has established a multiple regression model to easily calculate total skeletal SV (or TSSV) based on simple skeletal measurements obtained from a pelvic CT scan or radiograph. This model, based on data from only 20 cadavers, did not account for sex differences in TSSV. This study thus extends this work toward sex-specific models. METHODS: Twenty male and 20 female cadavers were subjected to whole-body CT. Bone sites containing active bone marrow were manually segmented to obtain SV at each site. In addition to age and height, 14 CT-based skeletal measurements were recorded for each cadaver. Multiple linear regression techniques were used to determine the best subset of measurements that allowed an accurate prediction of TSSV. RESULTS: A pooled model (R(2) = 0.76) and a sex-specific model (R(2) = 0.79) are provided. A leave-one-out analysis reveals that these models predict total SV with less than 10% error for 50%-70% of subjects, and with less than 20% error for 70%-90% of subjects. Tables were constructed that provide the percent distribution of SV in active-marrow containing bone sites for both males and females. CONCLUSION: This study provides models that can be used to simply, yet accurately, predict total SV in individuals within the clinical setting. The models require only 2 or 3 skeletal measurements that can be easily measured on a pelvic CT scan. Even though this study does not conclusively determine which model is best at predicting TSSV, the sex-specific model is most consistent at providing reasonable estimates of TSSV. This study also explains how the predictive TSSV model can be used to estimate patient-specific active bone marrow mass under the assumption of reference values of marrow volume fraction and bone marrow cellularity by skeletal site.

CT volumetry of the skeletal tissues.

Computed tomography (CT) is an important and widely used modality in the diagnosis and treatment of various cancers. In the field of molecular radiotherapy, the use of spongiosa volume (combined tissues of the bone marrow and bone trabeculae) has been suggested as a means to improve the patient-specificity of bone marrow dose estimates. The noninvasive estimation of an organ volume comes with some degree of error or variation from the true organ volume. The present study explores the ability to obtain estimates of spongiosa volume or its surrogate via manual image segmentation. The variation among different segmentation raters was explored and found not to be statistically significant (p value >0.05). Accuracy was assessed by having several raters manually segment a polyvinyl chloride (PVC) pipe with known volumes. Segmentation of the outer region of the PVC pipe resulted in mean percent errors as great as 15% while segmentation of the pipe's inner region resulted in mean percent errors within approximately 5%. Differences between volumes estimated with the high-resolution CT data set (typical of ex vivo skeletal scans) and the low-resolution CT data set (typical of in vivo skeletal scans) were also explored using both patient CT images and a PVC pipe phantom. While a statistically significant difference (p value <0.002) between the high-resolution and low-resolution data sets was observed with excised femoral heads obtained following total hip arthroplasty, the mean difference between high-resolution and low-resolution data sets was found to be only 1.24 and 2.18 cm3 for spongiosa and cortical bone, respectively. With respect to differences observed with the PVC pipe, the variation between the high-resolution and low-resolution mean percent errors was a high as approximately 20% for the outer region volume estimates and only as high as approximately 6% for the inner region volume estimates. The findings from this study suggest that manual segmentation is a reasonably accurate and reliable means for the in vivo estimation of spongiosa volume. This work also provides a foundation for future studies where spongiosa volumes are estimated by various raters in more comprehensive CT data