Skull phantom-based methodology to validate MRI co-registration accuracy for Gamma Knife radiosurgery.

PURPOSE: Target localization, for stereotactic radiosurgery (SRS) treatment with Gamma Knife, has become increasingly reliant on the co-registration between the planning MRI and the stereotactic cone-beam computed tomography (CBCT). Validating image registration between modalities would be particularly beneficial when considering the emergence of novel functional and metabolic MRI pulse sequences for target delineation. This study aimed to develop a phantom-based methodology to quantitatively compare the co-registration accuracy of the standard clinical imaging protocol to a representative MRI sequence that was likely to fail co-registration. The comparative methodology presented in this study may serve as a useful tool to evaluate the clinical translatability of novel MRI sequences. METHODS: A realistic human skull phantom with fiducial marker columns was designed and manufactured to fit into a typical MRI head coil and the Gamma Knife patient positioning system. A series of "optimized" 3D MRI sequences-T1 -weighted Dixon, T1 -weighted fast field echo (FFE), and T2 -weighted fluid-attenuated inversion recovery (FLAIR)-were acquired and co-registered to the CBCT. The same sequences were "compromised" by reconstructing without geometric distortion correction and re-collecting with lower signal-to-noise-ratio (SNR) to simulate a novel MRI sequence with poor co-registration accuracy. Image similarity metrics-structural similarity (SSIM) index, mean squared error (MSE), and peak SNR (PSNR)-were used to quantitatively compare the co-registration of the optimized and compromised MR images. RESULTS: The ground truth fiducial positions were compared to positions measured from each optimized image volume revealing a maximum median geometric uncertainty of 0.39 mm (LR), 0.92 mm (AP), and 0.13 mm (SI) between the CT and CBCT, 0.60 mm (LR), 0.36 mm (AP), and 0.07 mm (SI) between the CT and T1 -weighted Dixon, 0.42 mm (LR), 0.23 mm (AP), and 0.08 mm (SI) between the CT and T1 -weighted FFE, and 0.45 mm (LR), 0.19 mm (AP), and 1.04 mm (SI) between the CT and T2 -weighted FLAIR. Qualitatively, pairs of optimized and compromised image slices were compared using a fusion image where separable colors were used to differentiate between images. Quantitatively, MSE was the most predictive and SSIM the second most predictive metric for evaluating co-registration similarity. A clinically relevant threshold of MSE, SSIM, and/or PSNR may be defined beyond which point an MRI sequence should be rejected for target delineation based on its dissimilarity to an optimized sequence co-registration. All dissimilarity thresholds calculated using correlation coefficients with in-plane geometric uncertainty would need to be defined on a sequence-by-sequence basis and validated with patient data. CONCLUSION: This study utilized a realistic skull phantom and image similarity metrics to develop a methodology capable of quantitatively assessing whether a modern research-based MRI sequence can be co-registered to the Gamma Knife CBCT with equal or less than equal accuracy when compared to a clinically accepted protocol.

Single-Fraction Stereotactic Radiosurgery Versus Hippocampal-Avoidance Whole Brain Radiation Therapy for Patients With 10 to 30 Brain Metastases: A Dosimetric Analysis.

PURPOSE: To compare normal tissue dosimetry between hippocampal-avoidance whole brain radiation therapy (HA-WBRT) and stereotactic radiosurgery (SRS) in patients with 10 to 30 brain metastases, and to describe a novel SRS strategy we term Spatially Partitioned Adaptive RadiosurgEry (SPARE). METHODS AND MATERIALS: A retrospective review identified SRS treatment plans with >10 brain metastases located >5 mm from the hippocampi. Our Gamma Knife Icon (GKI) SPARE (GKI-Spr) technique treats multiple metastases with single-fraction SRS partitioned over consecutive days while limiting the total treatment time to ≤60 minutes per day. Hippocampal and normal brain dosimetry were compared among GKI-Spr, single-fraction single-day GKI (GKI-Sfr), and 30 Gy in 10 fractions HA-WBRT. Dose metrics were converted to equivalent dose in 2 Gy fractions. RESULTS: Ten cases were analyzed. Compared with HA-WBRT, GKI-Spr significantly reduced the median equivalent dose in 2 Gy fractions hippocampal maximum point dose, mean dose, and dose to 40% of the hippocampi (D40%) by 86%, 93%, and 93%, respectively, and similarly for GKI-Sfr by 81%, 92%, and 91%, respectively. The normal brain median mean dose was reduced by 95% with GKI-Spr and 94% with GKI-Sfr. Compared with GKI-Sfr, GKI-Spr further reduced all normal brain and hippocampal dose metrics (P ≤ .014). CONCLUSIONS: GKI yields superior hippocampal and normal brain dosimetry compared with HA-WBRT, and GKI-Spr results in further dosimetric advantages.

In Vivo Feasibility of Arterial Embolization with Permanent and Absorbable Suture: The FAIR-Embo Concept.

PURPOSE: Arterial embolization has been shown to be effective and safe for the management of bleeding, especially for postpartum and pelvic traumatic bleeding. We propose to evaluate the proof of concept of feasibility and effectiveness of arterial embolization with absorbable and non-absorbable sutures in a porcine model. MATERIALS AND METHODS: In the acute setting (n = 1), several different arteries (mesenteric, splenic, pharyngeal, kidney) were embolized using non-absorbable sutures (NAS): Mersutures™ braided sutures (polyethylene terephthalate). In the chronic setting (n = 3), only lower pole renal arteries were embolized. On the right side, NAS was used, whereas on the left side embolization was realized with absorbable suture (AS): Vicryl® braided suture (polyglactin 910). The chronic group was followed for 3 months. The pigs received contrast-enhanced CT the day before embolization (D-1), after the embolization (D0), at 1 month and 3 months after embolization (M1 and M3); digital subtraction angiography (DSA) was done at D0 and M3 and histological analysis at M3. RESULTS: All vascular targets were effectively embolized without any pre- or postoperative complications. Both DSAs and CTs at M3 showed a 100% recanalization rate for the AS embolization and a partial reversal rate for the NAS embolization. A renal hypotrophy in the embolized region was observed during both the M1 and M3 scans for both sutures (AS and NAS) with a clear hypotrophy for the NAS embolized kidney. CONCLUSION: Embolization by AS and NAS (FAIR-Embo) is a feasible and effective treatment which opens up the possibility of global use of this inexpensive and widely available embolization agent.

Onyx Migration Into the Anterior Spinal Artery During Lumbar Artery Embolisation: an Adverse Event.

INTRODUCTION: The impact of sequential lumbar and intercostal artery occlusion on the risk of spinal cord ischaemia was evaluated; however, an adverse event (paraplegia) was encountered, which resulted in study interruption. Investigations were carried out to understand the reasons for the paraplegia. REPORT: To develop a porcine model of spinal cord ischaemic preconditioning prior to extensive thoraco-abdominal aneurysm endovascular aortic repair, the lumbar arteries were selectively embolised with Onyx 5 days prior to an extended thoracic aortic stent graft. Six pigs were used in this preliminary work. Four cases of paraplegia secondary to accidental migration of Onyx to the anterior spinal artery from the lumbar arteries are reported. Histological analysis confirmed severe spinal ischaemic injury and the presence of Onyx particles in the anterior spinal artery. DISCUSSION: Onyx is used for lumbar artery embolisation in type II endoleak treatment after endovascular aortic repair, and while migration in lumbar arteries is frequent, the risk of spinal cord ischaemia has never been described. The current study demonstrates the risk of paraplegia following Onyx migration to the anterior spinal artery from the lumbar artery in an experimental model. Thus, Onyx treatment for type II endoleaks from lumbar arteries should be used cautiously.

A realistic phantom for validating MRI-based synthetic CT images of the human skull.

PURPOSE: To introduce a new realistic human skull phantom for the validation of synthetic CT images of cortical bone from ultra-short echo-time (UTE) sequences. METHODS: A human skull of an adult female was utilized as a realistic representation of skull cortical bone. The skull was stabilized in a special acrylic container and was filled with contrast agents that have T1 and T2 relaxation times similar to human brain. The phantom was MR scanned at 3T with UTE and T2 -weighted sequences, followed by CT. A clustering approach was developed to extract the cortical bone signal from MR images. T2∗ maps of the skull were calculated. Synthetic CT images of the bone were compared to cortical bone signal extracted from CT images and confounding factors, such as registration errors, were analyzed. RESULTS: Dice similarity coefficient (DSC) of UTE-detected cortical bone was 0.84 and gradually decreased with decreasing number of spokes. DSC did not significantly depend on echo-time. Registration errors were found to be significant confounding factors, with 25% decrease in DSC for consistent 2 mm error at each axis. CONCLUSION: This work introduced a new realistic human skull phantom, specifically for the evaluation and analysis of synthetic CT images of cortical bone.

Measurement of time delays in gated radiotherapy for realistic respiratory motions.

PURPOSE: Gated radiotherapy is used to reduce internal motion margins, escalate target dose, and limit normal tissue dose; however, its temporal accuracy is limited. Beam-on and beam-off time delays can lead to treatment inefficiencies and/or geographic misses; therefore, AAPM Task Group 142 recommends verifying the temporal accuracy of gating systems. Many groups use sinusoidal phantom motion for this, under the tacit assumption that use of sinusoidal motion for determining time delays produces negligible error. The authors test this assumption by measuring gating time delays for several realistic motion shapes with increasing degrees of irregularity. METHODS: Time delays were measured on a linear accelerator with a real-time position management system (Varian TrueBeam with RPM system version 1.7.5) for seven motion shapes: regular sinusoidal; regular realistic-shape; large (40%) and small (10%) variations in amplitude; large (40%) variations in period; small (10%) variations in both amplitude and period; and baseline drift (30%). Film streaks of radiation exposure were generated for each motion shape using a programmable motion phantom. Beam-on and beam-off time delays were determined from the difference between the expected and observed streak length. RESULTS: For the system investigated, all sine, regular realistic-shape, and slightly irregular amplitude variation motions had beam-off and beam-on time delays within the AAPM recommended limit of less than 100 ms. In phase-based gating, even small variations in period resulted in some time delays greater than 100 ms. Considerable time delays over 1 s were observed with highly irregular motion. CONCLUSIONS: Sinusoidal motion shapes can be considered a reasonable approximation to the more complex and slightly irregular shapes of realistic motion. When using phase-based gating with predictive filters even small variations in period can result in time delays over 100 ms. Clinical use of these systems for patients with highly irregular patterns of motion is not advised due to large beam-on and beam-off time delays.

Minimal portal vein stenosis is a promising preconditioning in living donor liver transplantation in porcine model.

BACKGROUND & AIMS: The main hindrance in promoting living donor liver transplantation remains the morbi-mortality risk for the donor. Considering the opposed remodeling influence of portal and hepatic artery flows, our working hypothesis was to identify a lobar portal vein stenosis capable of inducing a contralateral liver mass compensatory enlargement, without the downstream ipsilateral atrophic response. METHODS: Twenty-four pigs entered this study. Six of them were used to establish hemodynamic changes following a progressive left portal vein (LPV) stenosis, in blood flow, pressure and vessel diameter of the LPV, main portal vein and hepatic artery. Sixteen pigs were divided into 4 groups: sham operated animals, 20% LPV stenosis, 50% LPV stenosis, and 100% LPV stenosis. Daily liver biopsies were collected until post-operative day 5 to investigate liver regeneration and atrophy (Ki67, STAT3, LC3, and activated caspase 3) according to the degree of LPV stenosis. Finally, changes in liver volumetry after 20% LPVS were investigated. RESULTS: A 20% LPV stenosis led to dilatation of the hepatic artery and a subsequent four-fold increase in hepatic arterial flow. Concomitantly, liver regeneration was triggered in the non-ligated lobe and the cell proliferation peak, 5 days after surgery, was comparable to that obtained after total LPV ligation. Moreover, 20% LPV stenosis preconditioning did not induce left liver atrophy contrary to 50 and 100% LPV stenosis. CONCLUSIONS: A 20% LPV stenosis seems to be the adequate preconditioning to get the remnant liver of living donor ready to take on graft harvesting without atrophy of the future graft.

Measurement of cerebral blood volume in mouse brain regions using micro-computed tomography.

Micro-computed tomography (micro-CT) is an X-ray imaging technique that can produce detailed 3D images of cerebral vasculature. This paper describes the development of a novel method for using micro-CT to measure cerebral blood volume (CBV) in the mouse brain. As an application of the methodology, we test the hypotheses that differences in CBV exist over anatomical brain regions and that high energy demanding primary sensory regions of the cortex have locally elevated CBV, which may reflect a vascular specialization. CBV was measured as the percentage of tissue space occupied by a radio-opaque silicon rubber that fills the vasculature. To ensure accuracy of the CBV measurements, several innovative refinements were made to standard micro-CT specimen preparation and analysis procedures. Key features of the described method are vascular perfusion under controlled pressure, registration of the micro-CT images to an MRI anatomical brain atlas and re-scaling of micro-CT intensities to CBV units with selectable exclusion of major vessels. Histological validation of the vascular perfusion showed that the average percentage of vessels filled was 93+/-3%. Comparison of thirteen brain regions in nine mice revealed significant differences in CBV between regions (p<0.0001) while cortical maps showed that primary visual and auditory areas have higher CBV than primary somatosensory areas.