Frameless multimodal image guidance of localized convection-enhanced delivery of therapeutics in the brain

INTRODUCTION: Convection-enhanced delivery (CED) has been shown to be an effective method of administering macromolecular compounds into the brain that are unable to cross the blood-brain barrier. Because the administration is highly localized, accurate cannula placement by minimally invasive surgery is an important requisite. This paper reports on the use of an angiographic c-arm system which enables truly frameless multimodal image guidance during CED surgery. METHODS: A microcannula was placed into the striatum of five sheep under real-time fluoroscopic guidance using imaging data previously acquired by cone beam computed tomography (CBCT) and MRI, enabling three-dimensional navigation. After introduction of the cannula, high resolution CBCT was performed and registered with MRI to confirm the position of the cannula tip and to make adjustments as necessary. Adeno-associated viral vector-10, designed to deliver small-hairpin micro RNA (shRNAmir), was mixed with 2.0 mM gadolinium (Gd) and infused at a rate of 3 mul/min for a total of 100 mul. Upon completion, the animals were transferred to an MR scanner to assess the approximate distribution by measuring the volume of spread of Gd. RESULTS: The cannula was successfully introduced under multimodal image guidance. High resolution CBCT enabled validation of the cannula position and Gd-enhanced MRI after CED confirmed localized administration of the therapy. CONCLUSION: A microcannula for CED was introduced into the striatum of five sheep under multimodal image guidance. The non-alloy 300 mum diameter cannula tip was well visualized using CBCT, enabling confirmation of the position of the end of the tip in the area of interest

Quantitative analysis of high-resolution, contrast-enhanced, cone-beam CT for the detection of intracranial in-stent hyperplasia

BACKGROUND: Intracranial in-stent hyperplasia is a stroke-associated complication that requires routine surveillance. OBJECTIVE: To compare the results of in vivo experiments to determine the accuracy and precision of in-stent hyperplasia measurements obtained with modified C-arm contrast-enhanced, cone-beam CT (CE-CBCT) imaging with those obtained by \u27gold standard\u27 histomorphometry. Additionally, to carry out clinical analyses comparing this CE-CBCT protocol with digital subtraction angiography (DSA). METHODS: A non-binned CE-CBCT protocol (VasoCT) was used that acquires x-ray images with a small field-of-view and applies a full-scale reconstruction algorithm providing high-resolution three-dimensional (3D) imaging with 100 microm isotropic voxels. In an vivo porcine model, VasoCT cross-sectional area measurements were compared with gold standard vessel histology. VasoCT and DSA were used to calculate in-stent stenosis in 23 imaging studies. RESULTS: Porcine VasoCT cross-sectional stent, lumen, and in-stent hyperplasia areas strongly correlated with histological measurements (r(2)=0.97, 0.93, 0.90; slope=1.14, 1.07, and 0.76, respectively; p\u3c0.0001). Clinical VasoCT percentage stenosis correlated well with DSA percentage stenosis (r(2)=0.84; slope=0.76), and the two techniques were free of consistent bias (Bland-Altman, bias=3.29%; 95% CI -14.75% to 21.33%). An illustrative clinical case demonstrated the advantages of VasoCT, including 3D capability and non-invasive IV contrast administration, for detection of in-stent hyperplasia. CONCLUSIONS: C-arm VasoCT is a high-resolution 3D capable imaging technique that has been validated in an animal model for measurement of in-stent tissue growth. Successful clinical implementation of the protocol was performed in a small case series. already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

Quantitative evaluation of C-arm CT cerebral blood volume in a canine model of ischemic stroke

BACKGROUND AND PURPOSE: Previous studies have shown the feasibility of assessing qualitative CBV measurements in the angiography suite by using FPD-CBCT systems. We have investigated the correlation of FPD-CBCT CBV lesion volumes to the infarct volume. MATERIALS AND METHODS: Unilateral strokes were created in 7 adult dogs. MR imaging and FPD-CBCT data were obtained after MCA occlusion. FPD-CBCT CBV and ADC maps were generated for all subjects. The animals were sacrificed immediately following the last imaging study to measure infarct volume on histology. The reliability of FPD-CBCT-based lesion volume measurements was compared with those measured histologically by using regression and Bland-Altman analysis. RESULTS: The best correlation (R(2) = 0.72) between lesion volumes assessed with FPD-CBCT and histology was established with a threshold of mean healthy CBV - 2.5 x SD. These results were inferior to the correlation of lesion volumes measured with ADC and histology (R(2) = 0.99). Bland-Altman analysis showed that the agreement of ADC-derived lesion volumes with histology was superior to the agreement of FPD-CBCT-derived lesion volumes with histology. CONCLUSIONS: We correlated FPD-CBCT measurements of CBV and MR ADC lesion volumes with histologically assessed infarct volume. As expected, ADC is a very accurate and precise method for determining the extent of infarction. FPD-CBCT CBV lesion volumes are correlated to the size of the infarct. Improvement of FPD-CBCT image quality provides an opportunity to establish quantitative CBV measurement in the angiography suite

Chemical exchange saturation transfer effect in blood

PURPOSE: In this report, the feasibility of using blood as an agent for Chemical Exchange Saturation Transfer (CEST) effect is investigated. METHODS: The CEST effect of porcine blood samples was investigated on a 3.0 T MRI scanner using various power levels and on a 14.1 T NMR spectrometer. As a proof-of-concept that CEST can be used to image blood in vivo, the technique was applied in two locations of healthy human volunteers, namely, the femoral artery and the M1-segment of the middle cerebral artery. RESULTS: The blood sample experiments showed that maximum CEST Magnetization Transfer Ratio asymmetry (MTRasym ) values of approximately 12% were achieved, with likely contributions from multiple blood components. These findings were confirmed during the in vivo experiments where CEST signal of blood was clearly greater than surrounding muscular (2%) and brain tissue (3%). CONCLUSION: Ex vivo and in vivo results show that blood is a suitable CEST agent that generates sufficient CEST contrast relative to surrounding tissue

Target delineation for radiosurgery of a small brain arteriovenous malformation using high-resolution contrast-enhanced cone beam CT

Three years following endovascular embolization of a 3 mm ruptured arteriovenous malformation (AVM) of the left superior colliculus in a 42-year-old man, digital subtraction angiography showed continuous regrowth of the lesion. Thin-slice MRI acquired for treatment planning did not show the AVM nidus. The patient was brought back to the angiography suite for high-resolution contrast-enhanced cone beam CT (VasoCT) acquired using an angiographic c-arm system. The lesion and nidus were visualized with VasoCT. MRI, CT and VasoCT data were transferred to radiation planning software and mutually co-registered. The nidus was annotated for radiation on VasoCT data by an experienced neurointerventional radiologist and a dose/treatment plan was completed. Due to image registration, the treatment area could be directly adopted into the MRI and CT data. The AVM was completely obliterated 10 months following completion of the radiosurgery treatment

MR Imaging of Myeloperoxidase Activity in a Model of the Inflamed Aneurysm Wall

BACKGROUND AND PURPOSE: Although myeloperoxidase activity in vivo can be visualized by using noninvasive imaging, successful clinical translation requires further optimization of the imaging approach. We report a motion-sensitized driven-equilibrium MR imaging approach for the detection of a myeloperoxidase activity-specific gadolinium-containing imaging agent in experimental aneurysm models, which compensates for irregular blood flow, enabling vascular wall imaging in the aneurysm. MATERIALS AND METHODS: A phantom was built from rotational angiography of a rabbit elastase aneurysm model and was connected to a cardiac pulse duplicator mimicking rabbit-specific flow conditions. A T1-weighted turbo spin-echo-based motion-sensitized driven-equilibrium pulse sequence was optimized in vitro, including the addition of fat suppression and the selection of the velocity-encoding gradient parameter. The optimized sequence was applied in vivo to rabbit aneurysm models with and without inflammation in the aneurysmal wall. Under each condition, the aneurysms were imaged before and after intravenous administration of the imaging agent. The signal-to-noise ratio of each MR imaging section through the aneurysm was calculated. RESULTS: The motion-sensitized driven-equilibrium sequence was optimized to reduce flow signal, enabling detection of the myeloperoxidase imaging agent in the phantom. The optimized imaging protocol in the rabbit model of saccular aneurysms revealed a significant increase in the change of SNR from pre- to post-contrast MR imaging in the inflamed aneurysms compared with naive aneurysms and the adjacent carotid artery (P \u3c .0001). CONCLUSIONS: A diagnostic MR imaging protocol was optimized for molecular imaging of a myeloperoxidase-specific molecular imaging agent in an animal model of inflamed brain aneurysms

Temporal evolution of susceptibility artifacts from coiled aneurysms on MR angiography: an in vivo canine study

BACKGROUND AND PURPOSE: Intracranial aneurysms treated by coiling have a risk for recurrence, requiring surveillance imaging. MRA has emerged as an attractive technique for postcoiling aneurysm imaging. Previous research has evaluated MR imaging artifacts of the coil mass in vitro. Our aim in this study was to evaluate MR imaging artifacts of coiled aneurysms in vivo with time. MATERIALS AND METHODS: Four sidewall aneurysms were created in each of 4 dogs. Aneurysms were embolized receiving only 1 type of coils. After embolization, the animals were transferred to MR imaging, which included axial 3D TOF MRA (TEs, 3.5, 5, and 6.9 ms), phase-contrast MRA, and coronal CE-MRA. MR imaging studies were repeated at 1, 4, 6, 8, 14, and 28 weeks. We calculated an OEF: OEF = V(A)/V(CM), where the numerator represents the volume of the MR imaging artifacts and the denominator is the true volume of the coil mass measured by 3D RA. RESULTS: OEFs were largest immediately after embolization and showed a gradual decay until approximately 4 weeks, when there was stabilization of the size of the artifacts. By 4 weeks, there was mild coil compaction (average coil mass volume decrease of 7.8%); however, the OEFs decreased by 25% after 4 weeks (P \u3c .001). CONCLUSIONS: MR imaging susceptibility artifacts change with time, being maximal in the postembolization setting and decaying until 4 weeks. The clinical implications of this study are that baseline MRA for comparison with future imaging should be acquired at a minimum of 1 week after the procedure

Endovascular treatment of tandem vascular occlusions in acute ischemic stroke

BACKGROUND AND PURPOSE: Tandem vascular occlusions are an important cause of acute ischemic stroke (AIS) and present unique treatment challenges. We report our experience of managing a subset of AIS patients with extracranial vascular stenting/angioplasty and intracranial revascularization. METHODS: Consecutive patients who presented at three centers with AIS from tandem vascular occlusions confirmed by brain and neck CT imaging were included in the study. We retrospectively analyzed the patient demographics, National Institute of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score at the time of admission, treatment strategy, angiographic results using the Thrombolysis In Cerebral Infarction (TICI) score, and clinical and imaging follow-up. RESULTS: Twenty-eight patients were included. The mean NIHSS score at admission was 18. Extracranial carotid occlusions with a concomitant middle cerebral artery occlusion were seen in 89.3% of patients (n = 25) and vertebral artery combined with basilar artery lesions in 10.7% (n = 3). An antegrade approach (ie, treatment of the extracranial lesion first) was used in 24 patients (85.7%). Proximal occlusion recanalization was achieved usually with a stent (n = 27; 96.4%). Pursuant to intracranial revascularization techniques, greater than or equal to TICI 2A recanalization was seen in 96.4% of patients. An mRS score of less than or equal to 2 at 90 days was achieved in 56.5% of patients. CONCLUSIONS: Our study shows preliminary data from three centers on recanalization of tandem occlusions in patients presenting with AIS. There was a preference to revascularize the proximal occlusion using a stent followed by distal recanalization with mechanical thrombectomy, intra-arterial thrombolysis or a combination of these. This approach has low periprocedural complications and can achieve an excellent angiographic and clinical outcome