Modified brix model analysis of bone perfusion in subjects of varying bone mineral density

Abstract

Purpose: To apply pharmacokinetic modeling to the investigation of bone perfusion in subjects of varying bone mineral density. Materials and Methods:This study re-analyzed previous experimental data. A modified pharmacokinetic model was applied to data obtained from two prior studies of dynamic contrast-enhanced MR imaging of L3 vertebral body in 165 subjects (65 males, 100 females), classified into three groups (normal, osteopenia, and osteoporosis) according to bone mineral density. Three parameters, amplitude A, exchange rate (k ep ), and elimination rate (k el ), were obtained by fitting the signal intensity to the pharmacokinetic model. These parameters were compared across the three groups for males and females, respectively.Results: Perfusion parameters, amplitude A was found to be reduced in osteoporotic subjects with additional, though less pronounced, reductions found in the permeability constant (A*k ep ) and the elimination rate (k el ). Increased marrow fat content was found in osteoporotic bone, which helped to partially explain the observed reduction in interstitial space.Conclusion: By pharmacokinetic model, bone perfusion can be quantitatively analyzed with alteration in functional parameters related to microcirculation in subjects of varying bone mineral density. Developing bone marrow specific pharmacokinetic models should help to deepen knowledge of physiological and pathological perfusion changes occurring in bone. OSTEOPOROSIS IS THE most common metabolic bone disorder (1). Bone loss and structural deterioration of bone tissue begins from the time of peak bone mass accelerating in the elderly particularly in postmenopausal females. This loss and structural deterioration of bone proceeds until bone strength becomes sufficiently poor as to increase susceptibility to fracture at which stage the osteoporotic state has been reached. Clinical, epidemiological, and histological studies have indicated a link between vascular disease and osteoporosis (2-5). Dynamic contrast-enhanced MRI (DCE-MRI) provides a more direct measure of bone perfusion. Bone perfusion is a physiological process, which can be assessed by DCE-MRI. Bone perfusion refers to a diverse process dependent on factors such as tissue blood flow, capillary capacitance and permeability, interstitial diffusion, interstitial space volume, and venous return (6,7). DCE-MRI studies have shown how semi-quantitative perfusion parameters (enhancement maximum, E max , and enhancement slope, E slope ) are consistently reduced in osteopenic and osteoporotic bone compared with normal bone mineral density (BMD) subjects (8-10). These semiquantitative parameters are robust and easy to measure, but they are limited in the information they provide regarding the physiological processes affected. Knowledge of the physiological processes behind altered bone perfusion can be improved by obtaining a more detailed assessment of bone perfusion kinetics beyond that provided by E max and E slope . This more detailed evaluation can be obtained by pharmacokinetic...

Evaluation of perfusion-related and true diffusion in vertebral bone marrow: a preliminary study

“…In addition, we compared these diffusion parameters with BMD and FF, and a positive correlation between D* and BMD was observed, which indicated a possible connection between bone marrow perfusion and BMD. This finding is supported by the results of previous studies in which the vertebral blood flow was decreased significantly in osteoporotic patients compared with that in healthy subjects [17,[20][21][22], thereby suggesting that the decrease in bone marrow perfusion may contribute to a decrease in the BMD and an increased risk of compression fracture. Although F is also a perfusionrelated parameter, we found no significant correlation between F and BMD.…”

“…First, we did not find a significant correlation between D* and FF because only a small number of healthy subjects with moderate BMD and FF were included in this study. However, previous studies have shown a negative correlation between the perfusion parameter and the FF in the bone marrow [20,21]. Therefore, we recommend that further evaluation in subjects with a wider range of BMD and FF, including osteopenia and osteoporosis, be undertaken with a lager sample size to confirm the findings in this study.…”

“…Concerning the relationship between BMD and bone perfusion, several authors have reported that MRI-derived perfusion parameters of vertebral bone marrow were decreased significantly in osteoporotic subjects compared with those of normal subjects [17][18][19][20][21][22]. These results suggest that a decrease in vertebral blood flow may be associated with a decrease in the BMD.…”

Analysis of contrast-enhanced medical images.

“…Additionally, the BM provides no direct measure of capillary permeability and is applicable only under specific permeability-limiting conditions [181]. However, the vasculature permeability can be roughly estimated with the product of the amplitude parameter, A Brix , and the rate constant, k ep [146,182].…”

“…The BM, which is particularly attractive since the AIF need not be known a priori [216], has been used to study the brain [146,170] and breast tumors [217][218][219][220]. It is frequently used to analyze the contrast uptake patterns in other applications, including intracranial meningiomas [221], malignant pleural mesothelioma [222], cervical cancer [223] and its chemoradiotherapy outcome [216], colorectal [224] and liver tumors [225], prostate diseases [180,[226][227][228][229], and recently, bone perfusion [182].…”