Purpose

To assess the trabecular bone microstructure in the proximal femur of HIV-infected men compared to healthy controls using high-resolution MRI in combination with advanced post processing methods.

Introduction

Only recently, improvements in MRI hardware and pulse sequences allowed imaging of the proximal femur with high resolution and thus enabled the assessment of trabecular bone microstructure (1). Further increases in spatial resolution have been achieved in-vivo in recent years leading to voxel sizes as small as 234×234×500μm (2,3). MRI is currently the only in-vivo imaging method that allows the visualization of the fine trabecular bone structure in the proximal femur with adequate spatial resolution. This allows the analysis of the trabecular bone structure and important information in respect to bone strength can be deducted from these images, which is not captured by bone mineral density alone. Therefore, it is a very promising tool to evaluate bone strength at this important fracture site.

It has been established that Human Immunodeficiency Virus (HIV) infection and antiretroviral therapy (ART) are independent risk factors for osteoporosis and fragility fractures. However, bone mineral density (BMD) does not explain the higher prevalence of fractures in HIV-infected individuals. Trabecular bone microarchitecture might be an important factor for predicting bone strength and stratifying fracture risk in this population. As HIV-infected individuals live longer due to more effective treatment, the rate of fragility fractures will significantly increase in the near future. Thus, a tool to assess trabecular bone microstructure in the proximal femur early in the disease would be useful to determine fracture risk and enhance the management of patients. Thus, the scope of this work was to apply our developed imaging and postprocessing tools to analyze the bone structure of HIV-infected individuals and compare the results to healthy controls.

Methods

The study complied with HIPAA guidelines and written informed consent was obtained from all subjects. Eight HIV infected men and 11 age- and gender-matched healthy controls were recruited. High-resolution MRI of the proximal femur was performed on a 3 Tesla system (GE discovery MR750, GE Healthcare, Waukesha, WI) using an eight-channel phased array cardiac coil and a fully balanced 3D steady state free precession (bSSFP) sequence. Imaging parameters included TE=4.2 ms, readout bandwidth rBW=±62.5 kHz, TR=10 ms and a flip angle α=60° acquired in about 15 minutes scan time depending on coverage. Automatic coil correction was applied using nonparametric nonuniform intensity normalization (N3) (4). For analysis, we used advanced image registration techniques, allowing for the comparison of trabecular bone microstructural parameters at corresponding anatomic locations: (a) femoral head, (b) femoral neck, and (c) trochanteric region (5) between HIV infected men and healthy controls. Four MR-based trabecular microstructural parameters were analyzed at each region: fuzzy bone volume fraction (f-BVF), trabecular bone number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp) (6). Comparisons were done with two-tailed unpaired Student’s t-tests. Differences were considered significant at p<0.05.

Results

Figures 1a and 1b show coronal cross-sections of representative high resolution MR images of the proximal femur of a healthy control and an HIV infected patient, respectively, while Figures 1c and 1d show the anatomic regions analyzed in this study (femoral head, neck and trochanter). All microstructural bone parameters derived from MRI in the proximal femur showed significant decrement in the femoral head of HIV infected patients compared to healthy controls (Table 1). In the femoral neck only Tb.Th did not show significant difference. In the femoral trochanter, only Tb.Sp. showed significant differences. All significant differences indicated lower trabecular bone quality in HIV-infected men.

Conclusion

Using MR imaging along with advanced postprocessing methods as a new tool to analyze bone structure in the proximal femur, we found significant decrement in trabecular bone microstructure of the proximal femur in HIV-infected men compared to healthy controls. This could be important to identify individuals with increased fracture risk early in the disease and make patient specific treatment recommendations. We conclude that MRI can be an important imaging tool for the assessment of bone structure in HIV-infected subjects.