Michael R. Hardisty

Quantitative characterization of metastatic disease in the spine. Part I. Semiautomated segmentation using atlas-based deformable registration and the level set method

Quantitative assessment of metastatic disease in bone is often considered immeasurable and, as such, patients with skeletal metastases are often excluded from clinical trials. In order to effectively quantify the impact of metastatic tumor involvement in the spine, accurate segmentation of the vertebra is required. Manual segmentation can be accurate but involves extensive and time-consuming user interaction. Potential solutions to automating segmentation of metastatically involved vertebrae are demons deformable image registration and level set methods. The purpose of this study was to develop a semiautomated method to accurately segment tumor-bearing vertebrae using the aforementioned techniques. By maintaining morphology of an atlas, the demons-level set composite algorithm was able to accurately differentiate between trans-cortical tumors and surrounding soft tissue of identical intensity. The algorithm successfully segmented both the vertebral body and trabecular centrum of tumor-involved and healthy vertebrae. This work validates our approach as equivalent in accuracy to an experienced user.

Whole bone strain quantification by image registration: a validation study.

Quantification of bone strain can be used to better understand fracture risk, bone healing, and bone turnover. The objective of this work was to develop and validate an intensity matching image registration method to accurately measure and spatially resolve strain in vertebrae using microCT imaging. A strain quantification method was developed that used two sequential microCT scans, taken in loaded and unloaded configurations. The image correlation algorithm implemented was a multiresolution intensity matching deformable registration that found a series of affine mapping between the unloaded and loaded scans. Once the registration was completed, the displacement field and strain field were calculated from the mappings obtained. Validation was done in two distinct ways: the first was to look at how well the method could quantify zero strain; the second was to look at how the method was able to reproduce a known applied strain field. Analytically defined strain fields that linearly varied in space and strain fields resulting from finite element analysis were used to test the strain measurement algorithm. The deformable registration method showed very good agreement with all cases imposed, establishing a detection limit of 0.0004 strain and displaying agreement with the imposed strain cases (average R2=0.96). The deformable registration routine developed was able to accurately measure both strain and displacement fields in whole rat vertebrae. A rigorous validation of any strain measurement method is needed that reports on the ability of the routine to measure strain in a variety of strain fields with differing spatial extents, within the structure of interest.

Quantitative characterization of metastatic disease in the spine. Part II. Histogram-based analyses.

Radiological imaging is essential to the appropriate management of patients with bone metastasis; however, there have been no widely accepted guidelines as to the optimal method for quantifying the potential impact of skeletal lesions or to evaluate response to treatment. The current inability to rapidly quantify the response of bone metastases excludes patients with cancer and bone disease from participating in clinical trials of many new treatments as these studies frequently require patients with so-called measurable disease. Computed tomography (CT) can provide excellent skeletal detail with a sensitivity for the diagnosis of bone metastases. The purpose of this study was to establish an objective method to quantitatively characterize disease in the bony spine using CT-based segmentations. It was hypothesized that histogram analysis of CT vertebral density distributions would enable standardized segmentation of tumor tissue and consequently allow quantification of disease in the metastatic spine. Thirty two healthy vertebral CT scans were first studied to establish a baseline characterization. The histograms of the trabecular centrums were found to be Gaussian distributions (average root-mean-square difference=30 voxel counts), as expected for a uniform material. Intrapatient vertebral level similarity was also observed as the means were not significantly different (p > 0.8). Thus, a patient-specific healthy vertebral body histogram is able to characterize healthy trabecular bone throughout that individuals thoracolumbar spine. Eleven metastatically involved vertebrae were analyzed to determine the characteristics of the lytic and blastic bone voxels relative to the healthy bone. Lytic and blastic tumors were segmented as connected areas with voxel intensities between specified thresholds. The tested thresholds were mu-1.0 sigma, mu - 1.5 sigma, and mu - 2.0 sigma, for lytic and mu + 2.0 sigma, mu+3.0 siema, and mu + 3.5 sigma for blastic tissue where mu and sigma were taken from the Gaussian characterization of a healthy level within the same patient. The ideal lytic and blastic segmentation thresholds were determined to be mu-sigma and mu + 2 sigma, respectively. Using the optimized thresholds to segment tumor tissue, a quantitative characterization of disease is possible to calculate tumor volumes, disease severity, and temporal progression or treatment effect. Our proposed histogram-based method for characterizing spinal metastases shows great potential in extending the quantitative capacity of CT-based radiographic evaluations.

Functional and Anatomic Orientation of the Femoral Head

BackgroundFemoral neck geometry directly affects load transmission through the hip. Orientations may be described anatomically or using functional definitions that consider load transmission.Questions/purposesThis study introduces and applies a new method for characterizing functional femoral orientation based on the distribution of subchondral bone density in the femoral head and compares it with orientation measures generated via established anatomic landmark-based methods. Both orientation methods then are used to characterize side-to-side symmetry of orientation and differences between men and women within the population.Patients and MethodsA retrospective review of CT imaging data from 28 patients was performed. Anatomic orientation was determined using established two-dimensional and three-dimensional landmarking methods. Subchondral bone density maps were generated and used to define a density-weighted surface normal vector. Orientation angles generated by the three methods were compared, with side-to-side symmetry and differences between genders also investigated.ResultsThe three methods measured substantially different angles for anteversion and neck-shaft angle. Weak correlations were found between anatomic and functional orientation measures for neck-shaft angle only.ConclusionsNeck-shaft angles calculated using the functional orientation method corresponded well with previous in vivo loading data. An absence of strong correlation between functional and anatomic measures reinforces the concept that bone geometry is not solely responsible for determining loading of the femoral head.Level of Evidence Level II, Diagnostic Studies—Investigating a Diagnostic Test. See the Guidelines for Authors for a complete description of levels of evidence.

Micro-computed tomography–based highly automated 3D segmentation of the rat spine for quantitative analysis of metastatic disease

Noninvasive evaluation of metastatic disease in the spine has generally been limited to 2D qualitative or semiquantitative analysis techniques. This study aims to develop and evaluate a highly automated micro-CT-based quantitative analysis tool that can measure the architectural impact of metastatic involvement in whole vertebrae. Micro-CT analysis of rat whole vertebrae was conducted using a combination of demons deformable registration, level set curvature evolution, and intensity based thresholding techniques along with upsampling and edge enhancement techniques. The algorithm was applied to 6 lumbar vertebrae (L1-3) from 6 rnu/rnu rats (3 healthy rats and 3 with metastatic involvement). Osteolytic metastatic involvement was modeled via MT1 human breast cancer cells. Excellent volumetric concurrency was achieved in comparing the automated micro-CT-based segmentations of the whole vertebrae, trabecular centrums, and individual trabecular networks to manual segmentations (98.9%, 96.1%, and 98.3%, respectively; 6 specimens), and the automated segmentations were achieved in a fraction of the time. The algorithm successfully accounted for discontinuities in the cortical shell caused by vasculature and osteolytic destruction. As such, this work demonstrates the potential of this highly automated segmentation tool to permit rapid precise quantitative structural analysis of the spine with minimum user interaction in the analysis of both healthy and pathological (metastatically involved) vertebrae. Future optimization and the incorporation of lower-resolution imaging parameters may allow automated analysis of clinical CT-based measures in addition to preclinical micro-CT-based analyses of the structural impact and progression of pathological processes in the spine.

Quantification of the effect of osteolytic metastases on bone strain within whole vertebrae using image registration.

The vertebral column is the most frequent site of metastatic involvement of the skeleton with up to 1/3 of all cancer patients developing spinal metastases. Longer survival times for patients, particularly secondary to breast cancer, have increased the need for better understanding the impact of skeletal metastases on structural stability. This study aims to apply image registration to calculate strain distributions in metastatically involved rodent vertebrae utilizing µCT imaging. Osteolytic vertebral lesions were developed in five rnu/rnu rats 2–3 weeks post intracardiac injection with MT‐1 human breast cancer cells. An image registration algorithm was used to calculate and compare strain fields due to axial compressive loading in metastatically involved and control vertebrae. Tumor‐bearing vertebrae had greatly increased compressive strains, double the magnitude of strain compared to control vertebrae (p = 0.01). Qualitatively strain concentrated within the growth plates in both tumor bearing and control vertebrae. Most interesting was the presence of strain concentrations at the dorsal wall in metastatically involved vertebrae, suggesting structural instability. Strain distributions, quantified by image registration were consistent with known consequences of lytic involvement. Metastatically involved vertebrae had greater strain magnitude than control vertebrae. Strain concentrations at the dorsal wall in only the metastatic vertebrae, were consistent with higher incidence of burst fracture secondary to this pathology. Future use of image registration of whole vertebrae will allow focused examination of the efficacy of targeted and systemic treatments in reducing strains and the related risk of fracture in pathologic bones under simple and complex loading.

Effects of Photodynamic Therapy on the Structural Integrity of Vertebral Bone

Study Design. This study investigates the effects of photodynamic therapy (PDT) on the structural integrity of vertebral bone in healthy rats. Objective. To determine the short-term (1 week) and intermediate term (6 weeks) effects of a single PDT treatment on the mechanical and structural properties of vertebral bone. Summary of Background Data. Spinal metastasis develops in up to one-third of all cancer patients, compromising the mechanical integrity of the spine and thereby increasing the risk of pathologic fractures and spinal cord damage. PDT has recently been adapted to ablate metastatic tumors in the spine in preclinical animal models. However, little is known about the effects of PDT on the structural integrity of vertebral bone. Methods. A single PDT treatment was administered to healthy Wistar rats at photosensitizer and light doses known to be effective in athymic rats bearing human breast cancer metastases. At both 1 and 6 weeks posttreatment, changes in trabecular architecture, global stiffness and strength of vertebrae were quantified using micro-CT stereological analysis and axial compression testing. Results. At 6 weeks, there was a significant increase in bone volume fraction (to 55.7 ± 11.1% vs. 38.5 ± 6.4%, P < 0.001) and decrease in bone surface area-to-volume ratio (16.9 ± 5.0/mm vs. 22.8 ± 4.5/mm, P = 0.001), attributed to trabecular thickening (130 ± 40 &mgr;m vs. 90 ± 20 &mgr;m, P < 0.001). Similar trends were found at 1 week after PDT. There was a significant increase in stiffness from control (306 ± 123 N/mm) at 1 week (399 ± 150 N/mm, P = 0.04) and 6 weeks (410 ± 113 N/mm, P = 0.05) post PDT. There was a positive trend toward increased ultimate stress at 1 week, which became statistically significant at 6 weeks compared with control (39.3 ± 11.3 MPa vs. 27.5 ± 9.5 MPa control, P = 0.002). Conclusion. Not only may PDT be successful in ablating metastatic tumor tissue in the spine, but the positive effects of PDT on bone found in this study suggest that PDT may also improve vertebral mechanical stability.

Exploring the role of 3-dimensional simulation in surgical training: feedback from a pilot study.

Study Design Randomized control study assessing the efficacy of a pedicle screw insertion simulator. Objectives To evaluate the efficacy of an in-house developed 3-dimensional software simulation tool for teaching pedicle screw insertion, to gather feedback about the utility of the simulator, and to help identify the context and role such simulation has in surgical education. Summary of Background Data Traditional instruction for pedicle screw insertion technique consists of didactic teaching and limited hands-on training on artificial or cadaveric models before guided supervision within the operating room. Three- dimensional computer simulation can provide a valuable tool for practicing challenging surgical procedures; however, its potential lies in its effective integration into student learning. Methods Surgical residents were recruited from 2 sequential years of a spine surgery course. Patient and control groups both received standard training on pedicle screw insertion. The patient group received an additional 1-hour session of training on the simulator using a CT-based 3-dimensional model of their assigned cadavers spine. Qualitative feedback about the simulator was gathered from the trainees, fellows, and staff surgeons, and all pedicles screws physically inserted into the cadavers during the courses were evaluated through CT. Results A total of 185 thoracic and lumbar pedicle screws were inserted by 37 trainees. Eighty-two percent of the 28 trainees who responded to the questionnaire and all fellows and staff surgeons felt the simulator to be a beneficial educational tool. However, the 1-hour training session did not yield improved performance in screw placement. Conclusions A 3-dimensional computer-based simulation for pedicle screw insertion was integrated into a cadaveric spine surgery instructional course. Overall, the tool was positively regarded by the trainees, fellows, and staff surgeons. However, the limited training with the simulator did not translate into widespread comfort with its operation or into improvement in physical screw placement.

Acetabular orientation: anatomical and functional measurement

PurposeAcetabular orientation is important to consider in hip joint pathology and treatment. This study aims to describe the functional orientation of the acetabulum as a representative measure of force transmitted through the hip joint generated from bone density mapping and compare it to landmark-based anatomical orientation measures.MethodsCT scans of 38 non-pathologic individuals were analyzed. Functional orientation was computed as the density-weighted average of the acetabular surface normals based on surface density maps. Two anatomical measures were also used to describe the orientation of each acetabulum: the normal to the acetabular rim plane and the abduction angle based on AP pelvic “Radiographs” generated from the CT data.ResultsThe average functional and anatomic abduction and anteversion angles ranged from 32°–58° and 22°–31°, respectively, with significant side-to-side correlation in individual patients for the majority of measures. Functional acetabular orientation was weakly correlated only with the rim plane measure. Native acetabular abduction in the 3D anatomic and functional methods was significantly shallower than the 2D “Radiographic” measure. The vector generated to describe functional acetabular orientation was found to be more vertically and posteriorly oriented than the anatomic measures.ConclusionsFunctional acetabular orientation, reflecting the calculated directionality of the subchondral bone density, yields a more posterior and vertical measure of acetabular orientation as compared to the direction of load transmission suggested by the anatomic methods.

Importance of the dome and posterior wall as evidenced by bone density mapping in the acetabulum

BACKGROUND Characterizing the distribution of bone density in the acetabulum is of importance in better understanding and guiding treatment for both osteoarthritis and trauma of the hip joint. This study aims to develop a highly automated method to quantify the pattern of subchondral bone density in the acetabulum using clinically identifiable regions. METHODS Subchondral acetabular bone density distribution maps were created bilaterally from 30 non-pathologic pelvic CT scans. The density maps were aligned orthogonal to the acetabular rim plane and divided into twelve zones. Average bone density was calculated in each of these zones and compared to investigate differences between regions within each acetabulum and between right and left sides in a given patient. FINDINGS In all patients, the zones corresponding to the dome and posterior wall of the acetabulum demonstrated significantly higher average bone densities than all other regions (P<0.01). Significant correlations (R=0.4 to 0.76, P<0.05) were found between corresponding regions of the left and right sides in 10 of the 12 zones. INTERPRETATION The pattern of subchondral bone density distribution found in this study is consistent with previously observed bone density patterns in the acetabulum. Correspondence of right and left sides suggests that the distribution of loading on the acetabulum is similar on both sides in healthy individuals, though differences may exist in load sharing. Quantifying bone density patterns using zonal density map analysis may lead to a better understanding of the impact of traumatic injuries and progression of pathologic conditions in the hip joint.