Joseph E. Heiserman

Relative Cerebral Blood Volume Values to Differentiate High-Grade Glioma Recurrence from Posttreatment Radiation Effect: Direct Correlation between Image-Guided Tissue Histopathology and Localized Dynamic Susceptibility-Weighted Contrast-Enhanced Perfusion MR Imaging Measurements

BACKGROUND AND PURPOSE: Differentiating tumor growth from posttreatment radiation effect (PTRE) remains a common problem in neuro-oncology practice. To our knowledge, useful threshold relative cerebral blood volume (rCBV) values that accurately distinguish the 2 entities do not exist. Our prospective study uses image-guided neuronavigation during surgical resection of MR imaging lesions to correlate directly specimen histopathology with localized dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC) measurements and to establish accurate rCBV threshold values, which differentiate PTRE from tumor recurrence. MATERIALS AND METHODS: Preoperative 3T gradient-echo DSC and contrast-enhanced stereotactic T1-weighted images were obtained in patients with high-grade glioma (HGG) previously treated with multimodality therapy. Intraoperative neuronavigation documented the stereotactic location of multiple tissue specimens taken randomly from the periphery of enhancing MR imaging lesions. Coregistration of DSC and stereotactic images enabled calculation of localized rCBV within the previously recorded specimen locations. All tissue specimens were histopathologically categorized as tumor or PTRE and were correlated with corresponding rCBV values. All rCBV values were T1-weighted leakage-corrected with preload contrast-bolus administration and T2/T2*-weighted leakage-corrected with baseline subtraction integration. RESULTS: Forty tissue specimens were collected from 13 subjects. The PTRE group (n = 16) rCBV values ranged from 0.21 to 0.71, tumor (n = 24) values ranged from 0.55 to 4.64, and 8.3% of tumor rCBV values fell within the PTRE group range. A threshold value of 0.71 optimized differentiation of the histopathologic groups with a sensitivity of 91.7% and a specificity of 100%. CONCLUSIONS: rCBV measurements obtained by using DSC and the protocol we have described can differentiate HGG recurrence from PTRE with a high degree of accuracy.

PROPELLER MRI: Clinical testing of a novel technique for quantification and compensation of head motion

While head motion is considered a significant problem in magnetic resonance imaging (MRI), there is no data to quantify its extent, severity, or effect on image quality. PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) MRI offers a novel means of quantifying and compensating for head motion. We performed axial T2‐weighted PROPELLER (motion corrected: P‐CR; uncorrected: P‐UNCR) and conventional MRI (CONV), with equal scan times, in five normal volunteers and 35 clinical subjects. Volunteers were examined lying still and performing two separate head movements (shake “no” and nod “yes”) to assess detection and compensation of in‐plane motion by PROPELLER MRI. Images were examined by three radiologists for motion artifact and for overall image quality. Head rotation and translation was detected in all subjects during each slice acquisition, with expected changes occurring with volunteer head motion. Motion artifact was less commonly seen on PROPELLER than CONV MR (χ2 test P < 0.001). PROPELLER was preferred over CONV in all subjects (P < 0.05) and P‐CR was judged superior to P‐UNCR (P = 0.02). Intracranial pathology was equally or better demonstrated with PROPELLER. PROPELLER MRI offers a means of quantifying head motion, reducing motion artifact, and improving image quality. J. Magn. Reson. Imaging 2001;14:215–222.

Reevaluating the imaging definition of tumor progression: perfusion MRI quantifies recurrent glioblastoma tumor fraction, pseudoprogression, and radiation necrosis to predict survival

INTRODUCTION: Contrast-enhanced MRI (CE-MRI) represents the current mainstay for monitoring treatment response in glioblastoma multiforme (GBM), based on the premise that enlarging lesions reflect increasing tumor burden, treatment failure, and poor prognosis. Unfortunately, irradiating such tumors can induce changes in CE-MRI that mimic tumor recurrence, so called post treatment radiation effect (PTRE), and in fact, both PTRE and tumor re-growth can occur together. Because PTRE represents treatment success, the relative histologic fraction of tumor growth versus PTRE affects survival. Studies suggest that Perfusion MRI (pMRI)–based measures of relative cerebral blood volume (rCBV) can noninvasively estimate histologic tumor fraction to predict clinical outcome. There are several proposed pMRI-based analytic methods, although none have been correlated with overall survival (OS). This study compares how well histologic tumor fraction and OS correlate with several pMRI-based metrics. METHODS: We recruited previously treated patients with GBM undergoing surgical re-resection for suspected tumor recurrence and calculated preoperative pMRI-based metrics within CE-MRI enhancing lesions: rCBV mean, mode, maximum, width, and a new thresholding metric called pMRI–fractional tumor burden (pMRI-FTB). We correlated all pMRI-based metrics with histologic tumor fraction and OS. RESULTS: Among 25 recurrent patients with GBM, histologic tumor fraction correlated most strongly with pMRI-FTB (r = 0.82; P < .0001), which was the only imaging metric that correlated with OS (P<.02). CONCLUSION: The pMRI-FTB metric reliably estimates histologic tumor fraction (i.e., tumor burden) and correlates with OS in the context of recurrent GBM. This technique may offer a promising biomarker of tumor progression and clinical outcome for future clinical trials.

Correlations between Perfusion MR Imaging Cerebral Blood Volume, Microvessel Quantification, and Clinical Outcome Using Stereotactic Analysis in Recurrent High-Grade Glioma

BACKGROUND AND PURPOSE: Quantifying MVA rather than MVD provides better correlation with survival in HGG. This is attributed to a specific “glomeruloid” vascular pattern, which is better characterized by vessel area than number. Despite its prognostic value, MVA quantification is laborious and clinically impractical. The DSC-MR imaging measure of rCBV offers the advantages of speed and convenience to overcome these limitations; however, clinical use of this technique depends on establishing accurate correlations between rCBV, MVA, and MVD, particularly in the setting of heterogeneous vascular size inherent to human HGG. MATERIALS AND METHODS: We obtained preoperative 3T DSC-MR imaging in patients with HGG before stereotactic surgery. We histologically quantified MVA, MVD, and vascular size heterogeneity from CD34-stained 10-μm sections of stereotactic biopsies, and we coregistered biopsy locations with localized rCBV measurements. We statistically correlated rCBV, MVA, and MVD under conditions of high and low vascular-size heterogeneity and among tumor grades. We correlated all parameters with OS by using Cox regression. RESULTS: We analyzed 38 biopsies from 24 subjects. rCBV correlated strongly with MVA (r = 0.83, P < .0001) but weakly with MVD (r = 0.32, P = .05), due to microvessel size heterogeneity. Among samples with more homogeneous vessel size, rCBV correlation with MVD improved (r = 0.56, P = .01). OS correlated with both rCBV (P = .02) and MVA (P = .01) but not with MVD (P = .17). CONCLUSIONS: rCBV provides a reliable estimation of tumor MVA as a biomarker of glioma outcome. rCBV poorly estimates MVD in the presence of vessel size heterogeneity inherent to human HGG.

Anatomical and Biomechanical Analyses of the Unique and Consistent Locations of Sacral Insufficiency Fractures

Study Design. Correlation of locations of sacral insufficiency fractures is made to regions of stress depicted by finite element analysis derived from biomechanical models of patient activities. Objective. Sacral insufficiency fractures occur at consistent locations. It was postulated that sacral anatomy and sites of stress within the sacrum with routine activities in the setting of osteoporosis are foundations for determining patterns for the majority of sacral insufficiency fractures. Summary of Background Data. The predominant vertical components of sacral insufficiency fractures most frequently occur bilaterally through the alar regions of the sacrum, which are the thickest and most robust appearing portions of the sacrum instead of subjacent to the central sacrum, which bears the downward force of the spine. Methods. First, the exact locations of 108 cases of sacral insufficiency fractures were catalogued and compared to sacral anatomy. Second, different routine activities were simulated by pelvic models from CT scans of the pelvis and finite element analysis. Analyses were done to correlate sites of stress with activities within the sacrum and pelvis compared to patterns of sacral insufficiency fractures from 108 cases. Results. The sites of stress depicted by the finite element analysis walking model strongly correlated with identical locations for most sacral and pelvic insufficiency fractures. Consistent patterns of sacral insufficiency fractures emerged from the 108 cases and a biomechanical classification system is introduced. Additionally, alteration of walking mechanics and asymmetric sacral stress may alter the pattern of sacral insufficiency fractures noted with hip pathology (P = 0.002). Conclusion. Locations of sacral insufficiency fractures are nearly congruous with stress depicted by walking biomechanical models. Knowledge of stress locations with activities, cortical bone transmission of stress, usual fracture patterns, intensity of sacral stress with different activities, and modifiers of walking mechanics may aid medical management, interventional, or surgical efforts.

The radiographic and imaging characteristics of porous tantalum implants within the human cervical spine.

Study Design. Seven cadaveric cervical spines were implanted with a porous tantalum spacer and a titanium alloy spacer, and their radiographic and imaging characteristics were evaluated. Objective. To determine the radiographic characteristics of porous tantalum and titanium implants used as spacers in the cervical spine. Summary of Background Data. Anterior decompressive surgery of the disc space or the vertebral body creates a defect that frequently is repaired with autologous bone grafts to promote spinal fusion. Donor site morbidity, insufficient donor material, and additional surgical time have spurred the development of biomaterials to replace or supplement existing spinal reconstruction techniques. Although the promotion of a solid bony fusion is critical, the implanted biomaterial should be compatible with modern imaging techniques, should allow visualization of the spinal canal and neural foramina, and should permit radiographic assessment of bony ingrowth. Methods. Cadaveric spines containing the implants were imaged with plain radiography, computerized tomography, and magnetic resonance imaging. The image distortion produced by the implants was determined qualitatively and quantitatively. Results. The tantalum and titanium spacers were opaque on plain radiographic films. On computed tomographic scans, more streak artifact was associated with the tantalum implants than with the titanium. On magnetic resonance imaging, the porous tantalum implant demonstrated less artifact than did the titanium spacer on T1‐ and T2‐weighted spin echo and on T2*‐weighted gradient‐echo magnetic resonance images. Overall, the tantalum implant produced less artifact on magnetic resonance imaging than did the titanium spacer and therefore allowed for better visualization of the surrounding bony and neural structures. Conclusion. The material properties of titanium and porous tantalum cervical interbody implants contribute to their differential appearance in different imaging methods. The titanium implant appears to image best with computed tomography, whereas the porous tantalum implant produces less artifact than does the titanium implant on several magnetic resonance imaging sequences.

Titanium Aneurysm Clips: Part III Clinical Application in 16 Patients with Subarachnoid Hemorrhage

This report describes the first clinical use of newly developed titanium clips in the treatment of 16 patients with subarachnoid hemorrhage. There were no immediate or delayed complications related to the titanium clips. Thirteen patients had good outcomes, and one patient had moderate disabilities (mean follow-up, 5.4 mo). Two patients with Hunt and Hess Grade IV hemorrhages died postoperatively. The average cross-sectional areas of clip artifact on postoperative magnetic resonance imaging studies was 0.96, 1.36, and 1.05 cm2 on T1-, T2-, and intermediate-weighted images, respectively. In comparison, a matched control group with cobalt alloy clips had average cross-sectional areas of 3.13, 3.70, and 2.81 cm2 on T1-, T2-, and intermediate-weighted images, respectively. The average artifact volumes on gradient echo magnetic resonance images for titanium and cobalt alloy clips were 1.8 and 10.1 cm3, respectively. In addition, the gap on magnetic resonance imaging angiograms from clip artifacts was 0.9 cm with titanium and 2.6 cm with cobalt alloy clips. In conclusion, titanium aneurysm clips seem to be safe and effective and seem to reduce clip artifacts on magnetic resonance imaging threefold, compared with commercially available cobalt alloy clips. Because of this important advantage over conventional clips, titanium clips should be considered for routine use in aneurysm surgery.

Occipitocervical vertical distraction injuries: anatomical biomechanical, and 3-tesla magnetic resonance imaging investigation.

Study Design. Biomechanical load-to-failure findings correlated with anatomic dissection measurements and intact (prefailure) 3-Tesla (3-T) magnetic resonance images (MRI). Objective. To better understand why the same distractive force to the head can result in occipitoatlantal dislocation (OAD) in some individuals and atlantoaxial dislocation (AAD) in others. Summary of Background Data. Distraction injuries to the cranio-vertebral junction have been studied biomechanically but have not been studied relative to ligamentous anatomic variations. We theorized that morphologic variations in the ligaments should influence the injury pattern during axial distraction. Methods. After obtaining 3-T MRI scans, 10 occiput-C2 specimens were loaded to failure under axial tension. Direct anatomic measurements were also obtained from the distracted and injured specimens. Results. AAD was observed in 7 specimens (mean force ± standard deviation 1229 ± 181 N) at a significantly higher magnitude than OAD, which was observed in 3 specimens (823 ± 127 N; P = 0.009, nonpaired t test). In OAD specimens, the superior cruciate ligament (SCL), which was smaller than the inferior cruciate ligament (ICL), failed. The apical ligament was unidentifiable in these 3 specimens. In 5 of the 7 AAD specimens, the ICL ruptured and was smaller than the SCL. In the remaining 2 specimens, both SCL and ICL ruptured. The apical ligament, which ruptured, was identifiable in all 7 specimens. Conclusion. Axial distraction across the cranio-vertebral junction can produce either OAD or AAD. The SCL and ICL dimensions, alar ligament orientations, and apical ligament presence may affect the injury site. Visualization with 3-T MRI allows better understanding of the injury mechanism and location, which is important clinically in selecting single- or multilevel fixation.

Magnetic resonance imaging of the craniocervical junction at 3-T: observation of the accessory atlantoaxial ligaments.

OBJECTIVE:Instability of the craniocervical junction can cause neurological sequelae or pain. Stability of this region depends on extensive ligamentous support structures, most of which are well studied by magnetic resonance imaging (MRI) scanning. Although the contribution of the accessory atlantoaxial ligament to rotational stability has been described, this ligament has not been identified by imaging. Therefore, we investigated the imaging characteristics of this ligament and its relationship to the ligamentous complex of the craniocervical junction using the high resolution offered by 3-T MRI scans. METHODS:Ten healthy volunteers underwent MRI scanning at 3-T to determine the normal anatomy of this ligament. RESULTS:The atlantoaxial (C1–C2) segment of the ligament was identified in all 10 subjects bilaterally and symmetrically. Its mean dimensions were 2.8 × 1.8 mm. In four out of 10 subjects, the occipitoatlantal (C0–C1) segment was observed. At this level, the mean dimensions of the ligament were 1.6 × 1.2 mm on the right and 1.8 × 1.4 mm on the left. Its size varied between the right and left sides. CONCLUSION:The accessory atlantoaxial ligament can be visualized using high-resolution MRI scans at 3-T. The ligament was most consistent and robust at C1–C2. The ligament may, therefore, contribute to rotational stability at this level. Future studies will determine the biomechanical importance of this ligament, especially in the setting of trauma.

Perioperative ischemic complications of the brain after carotid endarterectomy.

BACKGROUNDThe potential morbidity of cerebral ischemia after carotid endarterectomy (CEA) has been recognized, but its reported incidence varies widely. OBJECTIVETo prospectively evaluate the development of cerebral ischemic complications in patients treated by CEA at a high-volume cerebrovascular center. METHODSFifty patients with moderate or severe carotid stenosis awaiting CEA were studied with perioperative diffusion-weighted imaging of the brain and standardized neurological evaluations. Microsurgical CEA was performed by 1 of 2 vascular neurosurgeons. Radiological studies were evaluated by faculty neuroradiologists who were blinded to the details of the clinical situation. RESULTSPreoperative diffusion-weighted imaging studies were performed within 24 hours of surgery. A second study was obtained within 24 (92% of patients), 48 (4% of patients), or 72 (4% of patients) hours after surgery. Intraluminal shunting was used in 1 patient (2%), and patch angioplasty was used in 2 patients (4%). No patient had diffusion-weighted imaging evidence of procedure-related cerebral ischemia. Nonischemic complications consisted of postoperative confusion in an 87-year-old man with a urinary tract infection and a marginal mandibular nerve paresis in another patient. Radiological studies were normal in both patients. CONCLUSIONCEA is a relatively safe procedure that may be performed with an acceptable risk of cerebral ischemia in select patients. The low rate of ischemic complications associated with CEA sets a standard to which other carotid revascularization techniques should be held. The current results are presented with a discussion of the senior authors preferred surgical technique and a brief review of the literature.