Assessment of histological characteristics, imaging markers, and rt-PA susceptibility of ex vivo venous thrombi.

Venous thromboembolism is a significant source of morbidity and mortality worldwide. Catheter-directed thrombolytics is the primary treatment used to relieve critical obstructions, though its efficacy varies based on the thrombus composition. Non-responsive portions of the specimen often remain in situ, which prohibits mechanistic investigation of lytic resistance or the development of diagnostic indicators for treatment outcomes. In this study, thrombus samples extracted from venous thromboembolism patients were analyzed ex vivo to determine their histological properties, susceptibility to lytic therapy, and imaging characteristics. A wide range of thrombus morphologies were observed, with a dependence on age and etymology of the specimen. Fibrinolytic inhibitors including PAI-1, alpha 2-antiplasmin, and TAFI were present in samples, which may contribute to the response venous thrombi to catheter-directed thrombolytics. Finally, a weak but significant correlation was observed between the response of the sample to lytic drug and its magnetic microstructure assessed with a quantitative MRI sequence. These findings highlight the myriad of changes in venous thrombi that may promote lytic resistance, and imaging metrics that correlate with treatment outcomes.

AAPM Task Group 241: A medical physicist's guide to MRI-guided focused ultrasound body systems.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a completely non-invasive technology that has been approved by FDA to treat several diseases. This report, prepared by the American Association of Physicist in Medicine (AAPM) Task Group 241, provides background on MRgFUS technology with a focus on clinical body MRgFUS systems. The report addresses the issues of interest to the medical physics community, specific to the body MRgFUS system configuration, and provides recommendations on how to successfully implement and maintain a clinical MRgFUS program. The following sections describe the key features of typical MRgFUS systems and clinical workflow and provide key points and best practices for the medical physicist. Commonly used terms, metrics and physics are defined and sources of uncertainty that affect MRgFUS procedures are described. Finally, safety and quality assurance procedures are explained, the recommended role of the medical physicist in MRgFUS procedures is described, and regulatory requirements for planning clinical trials are detailed. Although this report is limited in scope to clinical body MRgFUS systems that are approved or currently undergoing clinical trials in the United States, much of the material presented is also applicable to systems designed for other applications.

MRI-guided transurethral insonation of silica-shell phase-shift emulsions in the prostate with an advanced navigation platform.

PURPOSE: In this study, the efficacy of transurethral prostate ablation in the presence of silica-shell ultrasound-triggered phase-shift emulsions (sUPEs) doped with MR contrast was evaluated. The influence of sUPEs on MR imaging assessment of the ablation zone was also investigated. METHODS: sUPEs were doped with a magnetic resonance (MR) contrast agent, Gd2 O3 , to assess ultrasound transition. Injections of saline (sham), saline and sUPEs alone, and saline and sUPEs with Optison microbubbles were performed under guidance of a prototype interventional MRI navigation platform in a healthy canine prostate. Treatment arms were evaluated for differences in lesion size, T1  contrast, and temperature. In addition, non-perfused areas (NPAs) on dynamic contrast-enhanced (DCE) MRI, 55°C isotherms, and areas of 240 cumulative equivalent minutes at 43°C (CEM43 ) dose or greater computed from MR thermometry were measured and correlated with ablated areas indicated by histology. RESULTS: For treatment arms including sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area ranged from 0.96-0.99, 0.98-0.99, and 0.91-0.99, respectively. In the absence of sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area were 0.69, 0.54, and 0.50, respectively. Across all treatment arms, the areas of thermal tissue damage and NPAs were not significantly different (P = 0.47). Areas denoted by 55°C isotherms and 240 CEM43 dose boundaries were significantly larger than the areas of thermal damage, again for all treatment arms (P = 0.009 and 0.003, respectively). No significant differences in lesion size, T1 contrast, or temperature were observed between any of the treatment arms (P > 0.0167). Lesions exhibiting thermal fixation on histological analysis were present in six of nine insonations involving sUPE injections and one of five insonations involving saline sham injections. Significantly larger areas (P = 0.002), higher temperatures (P = 0.004), and more frequent ring patterns of restricted diffusion on ex vivo diffusion-weighted imaging (P = 0.005) were apparent in lesions with thermal fixation. CONCLUSIONS: T1 contrast suggesting sUPE transition was not evident in sUPE treatment arms. The use of MR imaging metrics to predict prostate ablation was not diminished by the presence of sUPEs. Lesions generated in the presence of sUPEs exhibited more frequent thermal fixation, though there were no significant changes in the ablation areas when comparing arms with and without sUPEs. Thermal fixation corresponded to some qualitative imaging features.

Comparison of arterial input functions measured from ultra-fast dynamic contrast enhanced MRI and dynamic contrast enhanced computed tomography in prostate cancer patients.

The purpose of this study was to evaluate the accuracy of arterial input functions (AIFs) measured from dynamic contrast enhanced (DCE) MRI following a low dose of contrast media injection. The AIFs measured from DCE computed tomography (CT) were used as 'gold standard'. A total of twenty patients received CT and MRI scans on the same day. Patients received 120 ml Iohexol in DCE-CT and a low dose of (0.015 mM kg-1) of gadobenate dimeglumine in DCE-MRI. The AIFs were measured in the iliac artery and normalized to the CT and MRI contrast agent doses. To correct for different temporal resolution and sampling periods of CT and MRI, an empirical mathematical model (EMM) was used to fit the AIFs first. Then numerical AIFs (AIFCT and AIFMRI) were calculated based on fitting parameters. The AIFMRI was convolved with a 'contrast agent injection' function ([Formula: see text]) to correct for the difference between MRI and CT contrast agent injection times (~1.5 s versus 30 s). The results show that the EMMs accurately fitted AIFs measured from CT and MRI. There was no significant difference (p > 0.05) between the maximum peak amplitude of AIFs from CT (22.1 ± 4.1 mM/dose) and MRI after convolution (22.3 ± 5.2 mM/dose). The shapes of the AIFCT and [Formula: see text] were very similar. Our results demonstrated that AIFs can be accurately measured by MRI following low dose contrast agent injection.

Comparison between whole-body and head and neck neurovascular coils for 3-T magnetic resonance proton resonance frequency shift thermography guidance in the head and neck region.

The purpose of this study is to compare the image quality of magnetic resonance (MR) treatment planning images and proton resonance frequency (PRF) shift thermography images and inform coil selection for MR-guided laser ablation of tumors in the head and neck region. Laser ablation was performed on an agar phantom and monitored via MR PRF shift thermography on a 3-T scanner, following acquisition of T1-weighted (T1W) planning images. PRF shift thermography images and T2-weighted (T2W) planning images were also performed in the neck region of five normal human volunteers. Signal-to-noise ratios (SNR) and temperature uncertainty were calculated and compared between scans acquired with the quadrature mode body integrated coil and a head and neck neurovascular coil. T1W planning images of the agar phantom produced SNRs of 4.0 and 12.2 for the quadrature mode body integrated coil and head and neck neurovascular coil, respectively. The SNR of the phantom MR thermography magnitude images obtained using the quadrature mode body integrated coil was 14.4 versus 59.6 using the head and neck coil. The average temperature uncertainty for MR thermography performed on the phantom with the quadrature mode body integrated coil was 1.1 versus 0.3 °C with the head and neck coil. T2W planning images of the neck in five human volunteers produced SNRs of 28.3 and 91.0 for the quadrature mode body integrated coil and head and neck coil, respectively. MR thermography magnitude images of the neck in the volunteers obtained using the quadrature mode body integrated coil had a signal-to-noise ratio of 8.3, while the SNR using the head and neck coil was 16.1. The average temperature uncertainty for MR thermography performed on the volunteers with the body coil was 2.5 versus 1.6 °C with the head and neck neurovascular coil. The quadrature mode body integrated coil provides inferior image quality for both basic treatment planning sequences and MR PRF shift thermography compared with a neurovascular coil, but may nevertheless be adequate for clinical purposes.

Implementation of a comprehensive MR safety course for medical students.

This review article proposes the design of an educational magnetic resonance (MR) safety course for instructing medical students about basic MR and patient-related safety. The MR safety course material can be implemented as a traditional didactic or interactive lecture in combination with hands-on safety demonstrations. The goal of the course is to ensure that medical students receive a basic understanding of MR principles and safety considerations. This course will prepare medical students for patient screening and safety consultations when ordering MR studies. A multiple-choice exam can be used to document the proficiency in MR safety of the medical students. The course can be used by various medical school programs and may help to ensure consistent quality of teaching materials and MR safety standards.

Short-term reproducibility of apparent diffusion coefficient estimated from diffusion-weighted MRI of the prostate.

PURPOSE: The purpose of the study is to determine short-term reproducibility of apparent diffusion coefficient (ADC) estimated from diffusion-weighted magnetic resonance (DW-MR) imaging of the prostate. METHODS: Fourteen patients with biopsy-proven prostate cancer were studied under an Institutional Review Board-approved protocol. Each patient underwent two, consecutive and identical DW-MR scans on a 3T system. ADC values were calculated from each scan and a deformable registration was performed to align corresponding images. The prostate and cancerous regions of interest (ROIs) were independently analyzed by two radiologists. The prostate volume was analyzed by sextant. Per-voxel absolute and relative percentage variations in ADC were compared between sextants. Per-voxel and per-ROI variations in ADC were calculated for cancerous ROIs. RESULTS: Per-voxel absolute difference in ADC in the prostate ranged from 0 to 1.60 × 10(-3) mm(2)/s (per-voxel relative difference 0% to 200%, mean 10.5%). Variation in ADC was largest in the posterior apex (0% to 200%, mean 11.6%). Difference in ADC variation between sextants was not statistically significant. Cancer ROIs' per-voxel variation in ADC ranged from 0.001 × 10(-3) to 0.841 × 10(-3) mm(2)/s (0% to 67.4%, mean 11.2%) and per-ROI variation ranged from 0 to 0.463 × 10(-3) mm(2)/s (mean 0.122 × 10(-3) mm(2)/s). CONCLUSIONS: Variation in ADC within the human prostate is reasonably small, and is on the order of 10%.

Cavernosal nerve functionality evaluation after magnetic resonance imaging-guided transurethral ultrasound treatment of the prostate.

AIM: To evaluate the feasibility of using therapeutic ultrasound as an alternative treatment option for organ-confined prostate cancer. METHODS: In this study, a trans-urethral therapeutic ultrasound applicator in combination with 3T magnetic resonance imaging (MRI) guidance was used for real-time multi-planar MRI-based temperature monitoring and temperature feedback control of prostatic tissue thermal ablation in vivo. We evaluated the feasibility and safety of MRI-guided trans-urethral ultrasound to effectively and accurately ablate prostate tissue while minimizing the damage to surrounding tissues in eight canine prostates. MRI was used to plan sonications, monitor temperature changes during therapy, and to evaluate treatment outcome. Real-time temperature and thermal dose maps were calculated using the proton resonance frequency shift technique and were displayed as two-dimensional color-coded overlays on top of the anatomical images. After ultrasound treatment, an evaluation of the integrity of cavernosal nerves was performed during prostatectomy with a nerve stimulator that measured tumescence response quantitatively and indicated intact cavernous nerve functionality. Planned sonication volumes were visually correlated to MRI ablation volumes and corresponding histo-pathological sections after prostatectomy. RESULTS: A total of 16 sonications were performed in 8 canines. MR images acquired before ultrasound treatment were used to localize the prostate and to prescribe sonication targets in all canines. Temperature elevations corresponded within 1 degree of the targeted sonication angle, as well as with the width and length of the active transducer elements. The ultrasound treatment procedures were automatically interrupted when the temperature in the target zone reached 56 °C. In all canines erectile responses were evaluated with a cavernous nerve stimulator post-treatment and showed a tumescence response after stimulation with an electric current. These results indicated intact cavernous nerve functionality. In all specimens, regions of thermal ablation were limited to areas within the prostate capsule and no damage was observed in periprostatic tissues. Additionally, a visual analysis of the ablation zones on contrast-enhanced MR images acquired post ultrasound treatment correlated excellent with the ablation zones on thermal dose maps. All of the ablation zones received a consensus score of 3 (excellent) for the location and size of the correlation between the histologic ablation zone and MRI based ablation zone. During the prostatectomy and histologic examination, no damage was noted in the bladder or rectum. CONCLUSION: Trans-urethral ultrasound treatment of the prostate with MRI guidance has potential to safely, reliably, and accurately ablate prostatic regions, while minimizing the morbidities associated with conventional whole-gland resection or therapy.

Validation of optimal DCE-MRI perfusion threshold to classify at-risk tumor imaging voxels in heterogeneous cervical cancer for outcome prediction.

PURPOSE: To classify tumor imaging voxels at-risk for treatment failure within the heterogeneous cervical cancer using DCE MRI and determine optimal voxel's DCE threshold values at different treatment time points for early prediction of treatment failure. MATERIAL AND METHOD: DCE-MRI from 102 patients with stage IB2-IVB cervical cancer was obtained at 3 different treatment time points: before (MRI 1) and during treatment (MRI 2 at 2-2.5 weeks and MRI 3 at 4-5 weeks). For each tumor voxel, the plateau signal intensity (SI) was derived from its time-SI curve from the DCE MRI. The optimal SI thresholds to classify the at-risk tumor voxels was determined by the maximal area under the curve using ROC analysis when varies SI value from 1.0 to 3.0 and correlates with treatment outcome. RESULTS: The optimal SI thresholds for MRI 1, 2 and 3 were 2.2, 2.2 and 2.1 for significant differentiation between local recurrence/control, respectively, and 1.8, 2.1 and 2.2 for death/survival, respectively. CONCLUSION: Optimal SI thresholds are clinically validated to quantify at-risk tumor voxels which vary with time. A single universal threshold (SI=1.9) was identified for all 3 treatment time points and remained significant for the early prediction of treatment failure.

Hybrid multidimensional T(2) and diffusion-weighted MRI for prostate cancer detection.

PURPOSE: To study the dependence of apparent diffusion coefficient (ADC) and T2 on echo time (TE) and b-value, respectively, in normal prostate and prostate cancer, using two-dimensional MRI sampling, referred to as "hybrid multidimensional imaging." MATERIALS AND METHODS: The study included 10 patients with biopsy-proven prostate cancer who underwent 3 Tesla prostate MRI. Diffusion-weighted MRI (DWI) data were acquired at b = 0, 750, and 1500 s/mm(2) . For each b-value, data were acquired at TEs of 47, 75, and 100 ms. ADC and T2 were measured as a function of b-value and TE, respectively, in 15 cancer and 10 normal regions of interest (ROIs). The Friedman test was used to test the significance of changes in ADC as a function of TE and of T2 as a function of b-value. RESULTS: In normal prostate ROIs, the ADC at TE of 47 ms is significantly smaller than ADC at TE of 100 ms (P = 0.0003) and T2 at b-value of 0 s/mm(2) is significantly longer than T2 at b-value of 1500 s/mm(2) (P = 0.001). In cancer ROIs, average ADC and T2 values do not change as a function of TE and b-value, respectively. However, in many cancer pixels, there are large decreases in the ADC as a function of TE and large increases in T2 as a function of b-value. Cancers are more conspicuous in ADC maps at longer TEs. CONCLUSION: Parameters derived from hybrid imaging that depend on coupled/associated values of ADC and T2 may improve the accuracy of MRI in diagnosing prostate cancer.

Prostate volumes derived from MRI and volume-adjusted serum prostate-specific antigen: correlation with Gleason score of prostate cancer.

OBJECTIVE: The purpose of this article is to study relationships between MRI-based prostate volume and volume-adjusted serum prostate-specific antigen (PSA) concentration estimates and prostate cancer Gleason score. MATERIALS AND METHODS: The study included 61 patients with prostate cancer (average age, 63.3 years; range 52-75 years) who underwent MRI before prostatectomy. A semiautomated and MRI-based technique was used to estimate total and central gland prostate volumes, central gland volume fraction (central gland volume divided by total prostate volume), PSA density (PSAD; PSA divided by total prostate volume), and PSAD for the central gland (PSA divided by central gland volume). These MRI-based volume and volume-adjusted PSA estimates were compared with prostatectomy specimen weight and Gleason score by using Pearson (r) or Spearman (ρ) correlation coefficients. RESULTS: The estimated total prostate volume showed a high correlation with reference standard volume (r = 0.94). Of the 61 patients, eight (13.1%) had a Gleason score of 6, 40 (65.6%) had a Gleason score of 7, seven (11.5%) had a Gleason score of 8, and six (9.8%) had a Gleason score of 9 for prostate cancer. The Gleason score was significantly correlated with central gland volume fraction (ρ = -0.42; p = 0.0007), PSAD (ρ = 0.46; p = 0.0002), and PSAD for the central gland (ρ = 0.55; p = 0.00001). CONCLUSION: Central gland volume fraction, PSAD, and PSAD for the central gland estimated from MRI examinations show a modest but significant correlation with Gleason score and have the potential to contribute to personalized risk assessment for significant prostate cancer.

Microcirculatory fraction (MCF(I)) as a potential imaging marker for tumor heterogeneity in breast cancer.

Cancer is a heterogeneous disease by nature. Current imaging studies usually ignore intratumor variability in imaging biomarkers. We postulate that quantifying tumor heterogeneity with imaging techniques can provide useful information about cancer biology and potentially serve as novel imaging biomarkers. In this retrospective study, we identify a potential imaging marker, the microcirculatory fraction (MCF(I)), that quantifies tumor heterogeneity in normoxic/hypoxic cellular composition. We demonstrate its application on a test population of 22 women with stage II/III HER-2 negative breast cancer receiving antiangiogenic-cytotoxic combination neoadjuvant chemotherapy. Early change in MCF(I) (ΔMCF(I)) is assessed with dynamic contrast enhanced magnetic resonance imaging at the end of Cycle 2 and associated with pathologic response. Its performance is compared with other established volumetric imaging biomarkers (initial tumor volume and volume change) by statistical and graphic methods. We demonstrate that a significant (P<.01) difference in ΔMCF(I) can be detected between good (median ΔMCF(I) 0.27) and poor (median ΔMCF(I) -0.12) responders, despite the limited population size. Differences in the volumetric biomarkers are not statistically significant. Receiver operating characteristic analysis also shows that ΔMCF(I) is a good predictor for pathologic response (AUC=0.86, 95% CI 0.69-1.00, P<.01), while predictions made with the established volumetric biomarkers are not significantly better than random guesses. We conclude that ΔMCF(I) has the potential of being a better predictive biomarker for therapeutic response assessment. Our findings support our postulation that quantifying tumor heterogeneity with imaging techniques can provide additional information that can serve as novel biomarkers.

Effect of registration mode on neuronavigation precision: an exploration of the role of random error.

The aim of this paper is to analyze the variations in registration accuracy for computer-assisted surgical navigation using three different modes of registration, in order to explore the behavior of random error, and to highlight the precision of neuronavigation as a concept distinct from accuracy. The operational accuracy of three different registration modes (bone fiducials, scalp adhesive fiducials and an auto-registration mask) was evaluated in a total of 20 fresh cadaveric heads. The precision of the neuronavigation system was then assessed by evaluating the variation in the accuracy measurements associated with each registration mode. The coefficient of variation was employed to quantify the degree of variation in the attained accuracy using the following formula: Coefficient of variation = standard deviation/mean * 100. For external targets, the precision of the neuronavigation system was greatest with mask registration (43.75 and 51.41 for anterior and posterior external targets, respectively) and lowest with bone registration (65.30 and 67.17 for anterior and posterior external targets, respectively). For internal targets, the precision of the neuronavigation system was greatest with bone registration (47.69 and 42.6 for anterior and posterior internal targets, respectively) and lowest with mask registration (62.9 and 58.67 for anterior and posterior internal targets, respectively). The precision (reproducibility) of the neuronavigation system is another important quantity besides accuracy that characterizes the performance of the system. Understanding both of these quantities for a given registration mode enhances the use of a neuronavigation system in neurosurgery.

Characterizing tumor heterogeneity with functional imaging and quantifying high-risk tumor volume for early prediction of treatment outcome: cervical cancer as a model.

PURPOSE: Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome. METHODS AND MATERIALS: DCE-MRI was performed in 102 stage IB(2)-IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the total volume of tumor voxels with critically low DCE signal intensity (<2.1 compared with precontrast image, determined by previous receiver operator characteristic analysis). FRVs were correlated with treatment outcome (follow-up: 0.2-9.4, mean 6.8 years) and compared with ATVs (Mann-Whitney, Kaplan-Meier, and multivariate analyses). RESULTS: Before and during therapy at 2-2.5 and 4-5 weeks of RT, FRVs >20, >13, and >5 cm(3), respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 × 10(-8), 2.0 × 10(-8)) and disease-specific survival (p = 1.9 × 10(-4), 2.1 × 10(-6), 2.5 × 10(-7), respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment. DISCUSSION: Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2-5 weeks into treatment.

A new methodology for laboratory evaluation of neurosurgical approaches based on the volume and shape of the surgical space with a mathematical model to quantify the surgical maneuverability in laboratory settings.

We conducted this study to validate the volume/shape of the surgical exposure and to introduce a mathematical model to quantify the maneuverability in a surgical space. We executed the pterional and lateral supraorbital approach four times in fresh cadavers in skull base laboratory. The surgical volumes were filled with a computed tomography (CT)-imageable mixture; CT scans were obtained to evaluate the volume and shape of the surgical space. The volume of the surgical space was 23.60 and 32.90 mL for the lateral supraorbital and pterional approach, respectively, (p < 0.05). The three-dimensional shape of the lateral supraorbital approach was cylindrical and that of the pterional approach pyramidal. The volume of the surgical approach can be used to define, together with other variables, the maneuverability (maneuvering in a surgical volume) by using the following formula [Formula: see text] where M, A, V, and L represent the maneuverability, the degree of the surgical freedom, the volume of the surgical exposure, and the surgical depth, respectively. Volume and shape of the surgical exposure are two objective parameters that can be used to define and contrast different microsurgical approaches in a laboratory setting. The volume of the surgical exposure may be integrated into a mathematical formula defining maneuverability.

Amide proton transfer MR imaging of prostate cancer: a preliminary study.

PURPOSE: To evaluate the capability of amide proton transfer (APT) MR imaging for detection of prostate cancer that typically shows a higher tumor cell proliferation rate and cellular density leading to an MRI-detectable overall elevated mobile protein level in higher grade tumors. MATERIALS AND METHODS: Twelve patients with biopsy-proven prostate cancer were imaged on a 3 Tesla MR imaging system before prostatectomy. APT-MR images were acquired by means of a single-slice single-shot turbo spin echo sequence with a saturation prepulse preparation using 33 different frequency offsets (-8 to 8 ppm, interval 0.5 ppm). For quantification we used the APT ratio (APTR) based on the asymmetry of the magnetization transfer ratio at 3.5 ppm in respect to the water signal. Tumor and peripheral zone benign regions of interest (ROIs) were delineated based on whole mount pathology slides after prostatectomy. RESULTS: APTR in prostate cancer ROIs was 5.8% ± 3.2%, significantly higher than that in the peripheral zone benign regions (0.3% ± 3.2%, P = 0.002). CONCLUSION: APT-MR imaging is feasible in prostate cancer detection and has the potential to discriminate between cancer and noncancer tissues.

Qualitative and quantitative radio-anatomical variation of the posterior clinoid process.

This study was conducted to investigate the radiological anatomy of the posterior clinoid process (PCP) to highlight preoperative awareness of its variations and its relationships to other skull base landmarks. The PCPs of 36, three-dimensional computed tomographic cadaveric heads were evaluated by studying the gross anatomy of the PCP and by measuring the distances between the PCP and other skull base anatomical landmarks relevant to transnasal or transcranial skull base approaches. PCP variations were found in five specimens (14%): in two the dorsum sellae was absent, in one the PCP and the anterior clinoid process (ACP) were connected unilaterally and in two bilaterally. The mean distance between the right/left PCP and the crista galli was 45.14 ± 4.0 standard deviation (SD_/46.24 ± 4.5 SD, respectively, while the distance to the middle point of the basion at the level of the foramen magnum was 40.41 ± 5.1 SD/41.0 ± 5.2 SD, respectively. The mean distance between the PCP and the ACP was 12.03 ± 3.18 SD on the right side and 12.11 ± 2.77 SD on the left. The data provided highlights the importance of careful preoperative evaluation of the PCP and of its relationships to other commonly encountered skull base landmarks. This information may give an idea of the exposure achievable through different transcranial and transnasal approaches. This is especially relevant when neuronavigation is not available.

Accuracy validation in a cadaver model of cranial neuronavigation using a surface autoregistration mask.

BACKGROUND: Image guidance systems are widely used in neurosurgical practice. OBJECTIVE: To compare the operational accuracy of a neuronavigation system when registration was accomplished with a commercially available surface-based autoregistration system vs other fiducial-based registrations. METHODS: We evaluated the operational accuracy of different registration methods in 20 cadaveric heads. Every specimen was prepared with 10 titanium microscrews functioning as external/internal targets and as bone fiducials. Six scalp fiducials were also affixed to each specimen that was registered with bone, scalp fiducials, and the autoregistration mask. The coordinates of all the target points were measured, first manually on the screen of the navigation system and then by touching the head of the implanted screw on the specimen. The difference between the real and virtual coordinates was calculated. RESULTS: Means of the differences for external anterior targets were 1.96, 3.12, and 3.20 mm and 1.95, 3.24, and 3.19 mm for external posterior targets for the bone fiducials, adhesive fiducials, and autoregistration mask, respectively. Means of the differences for internal anterior targets were 2.60, 3.65, and 2.16 mm and 2.91, 3.83, and 2.41 mm for internal posterior targets for the bone fiducials, adhesive fiducials, and autoregistration mask, respectively. CONCLUSION: Bone fiducial registration is associated with a statistically greater operational accuracy than scalp adhesive fiducials and the autoregistration mask in reaching anterior and posterior external targets (P < .001). Registration accomplished with the autoregistration mask is associated with a statistically greater operational accuracy in reaching internal targets than adhesive fiducials registration (P < .001) or bone fiducials registration (P < .05 and P < .01 for anterior and posterior targets, respectively).

Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer.

PURPOSE: Mutations in the RET proto-oncogene and vascular endothelial growth factor receptor (VEGFR) activity are critical in the pathogenesis of medullary thyroid cancer (MTC). Sorafenib, a multikinase inhibitor targeting Ret and VEGFR, showed antitumor activity in preclinical studies of MTC. PATIENTS AND METHODS: In this phase II trial of sorafenib in patients with advanced MTC, the primary end point was objective response. Secondary end points included toxicity assessment and response correlation with tumor markers, functional imaging, and RET mutations. Using a two-stage design, 16 or 25 patients were to be enrolled onto arms A (hereditary) and B (sporadic). Patients received sorafenib 400 mg orally twice daily. RESULTS: Of 16 patients treated in arm B, one achieved partial response (PR; 6.3%; 95% CI, 0.2% to 30.2%), 14 had stable disease (SD; 87.5%; 95% CI, 61.7% to 99.5%), and one was nonevaluable. In a post hoc analysis of 10 arm B patients with progressive disease (PD) before study, one patient had PR of 21+ months, four patients had SD >or= 15 months, four patients had SD