Percutaneous Image-Guided Cryoablation of Head and Neck Tumors for Local Control, Preservation of Functional Status, and Pain Relief.

OBJECTIVE: We report nine consecutive percutaneous image-guided cryoablation procedures of head and neck tumors in seven patients (four men and three women; mean age, 68 years; age range, 50-78 years). Ablation of the entire tumor for local control or ablation of a region of tumor for pain relief or preservation of function was achieved in eight of nine procedures. One patient experienced intraprocedural bradycardia, and another developed a neopharyngeal abscess. There were no deaths, permanent neurologic or functional deficits, vascular complications, or adverse cosmetic sequelae due to the procedures. CONCLUSION: Percutaneous image-guided cryoablation offers a potentially less morbid minimally invasive treatment option than salvage head and neck surgery. The complications that we encountered may be avoidable with increased experience. Further work is needed to continue improving the safety and efficacy of cryoablation of head and neck tumors and to continue expanding the use of cryoablation in patients with head and neck tumors that cannot be treated surgically.

Computer-Based Vertebral Tumor Cryoablation Planning and Procedure Simulation Involving Two Cases Using MRI-Visible 3D Printing and Advanced Visualization.

OBJECTIVE: We report the development and use of MRI-compatible and MRI-visible 3D printed models in conjunction with advanced visualization software models to plan and simulate safe access routes to achieve a theoretic zone of cryoablation for percutaneous image-guided treatment of a C7 pedicle osteoid osteoma and an L1 lamina osteoblastoma. Both models altered procedural planning and patient care. CONCLUSION: Patient-specific MRI-visible models can be helpful in planning complex percutaneous image-guided cryoablation procedures.

Clinical Validation of Automatable Gaussian Normalized CBV in Brain Tumor Analysis: Superior Reproducibility and Slightly Better Association with Survival than Current Standard Manual Normal Appearing White Matter Normalization.

PURPOSE: To validate Gaussian normalized cerebral blood volume (GN-nCBV) by association with overall survival (OS) in newly diagnosed glioblastoma patients and compare this association with current standard white matter normalized cerebral blood volume (WN-nCBV). METHODS: We retrieved spin-echo echo-planar dynamic susceptibility contrast MRI acquired after maximal resection and prior to radiation therapy between 2006 and 2011 in 51 adult patients (28 male, 23 female; age 23-87 years) with newly diagnosed glioblastoma. Software code was developed in house to perform Gaussian normalization of CBV to the standard deviation of the whole brain CBV. Three expert readers manually selected regions of interest in tumor and normal-appearing white matter on CBV maps. Receiver operating characteristics (ROC) curves associating nCBV with 15-month OS were calculated for both GN-nCBV and WN-nCBV. Reproducibility and interoperator variability were compared using within-subject coefficient of variation (wCV) and intraclass correlation coefficients (ICCs). RESULTS: GN-nCBV ICC (≥0.82) and wCV (≤21%) were superior to WN-nCBV ICC (0.54-0.55) and wCV (≥46%). The area under the ROC curve analysis demonstrated both GN-nCBV and WN-nCBV to be good predictors of OS, but GN-nCBV was consistently superior, although the difference was not statistically significant. CONCLUSION: GN-nCBV has a slightly better association with clinical gold standard OS than conventional WM-nCBV in our glioblastoma patient cohort. This equivalent or superior validity, combined with the advantages of higher reproducibility, lower interoperator variability, and easier automation, makes GN-nCBV superior to WM-nCBV for clinical and research use in glioma patients. We recommend widespread adoption and incorporation of GN-nCBV into commercial dynamic susceptibility contrast processing software.

Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction.

Ischemia resulting from myocardial infarction (MI) promotes VEGF expression, leading to vascular permeability (VP) and edema, a process that we show here contributes to tissue injury throughout the ventricle. This permeability/edema can be assessed noninvasively by MRI and can be observed at the ultrastructural level as gaps between adjacent endothelial cells. Many of these gaps contain activated platelets adhering to exposed basement membrane, reducing vessel patency. Following MI, genetic or pharmacological blockade of Src preserves endothelial cell barrier function, suppressing VP and infarct volume, providing long-term improvement in cardiac function, fibrosis, and survival. To our surprise, an intravascular injection of VEGF into healthy animals, but not those deficient in Src, induced similar endothelial gaps, VP, platelet plugs, and some myocyte damage. Mechanistically, we show that quiescent blood vessels contain a complex involving Flk, VE-cadherin, and beta-catenin that is transiently disrupted by VEGF injection. Blockade of Src prevents disassociation of this complex with the same kinetics with which it prevents VEGF-mediated VP/edema. These findings define a molecular mechanism to account for the Src requirement in VEGF-mediated permeability and provide a basis for Src inhibition as a therapeutic option for patients with acute MI.

Quantification of radiation dose reduction by reducing z-axis coverage in 320-detector coronary CT angiography.

OBJECTIVE: To quantify the radiation dose reduction achievable by minimizing z-axis coverage in 320-detector coronary CT angiography (CCTA). METHODS: We retrospectively reviewed 130 CCTAs performed on 320-detector CT that offers up to 16 cm z-axis coverage (adjustable in 2-cm increments), allowing complete coverage of the heart in a single gantry rotation. For each CT, we obtained the radiation dose [CT dose index and dose-length product (DLP)], measured the z-axis field of view and measured the craniocaudal cardiac size (distance from the left main coronary artery to the cardiac apex). We calculated the radiation dose savings achievable by reducing the z-axis coverage to the minimum necessary to cover the heart using 320 × 0.5-mm (maximum 16 cm) and 256 × 0.5-mm (maximum 12.8 cm) detector collimations. RESULTS: Results are expressed as mean ± standard deviation. The mean craniocaudal cardiac size was 10.5 ± 1.0 cm, with 85% (n = 112) of CCTAs performed with 16 cm of z-axis coverage. The mean DLP was 417.6 ± 182.4 mGy cm, with the mean DLP saving achievable using the minimum z-axis coverage required to completely image the heart being 96.2 ± 47.4 mGy cm, an average dose reduction of 26.9 ± 7.0%. z-axis coverage of ≤12 cm was adequate for 92% and 12.8 cm for 98% of subjects. CONCLUSION: Using the minimal z-axis coverage to adequately image the heart is a simple step that can reduce the DLP in 320-detector CCTA by approximately 27%. z-axis coverage of ≤12 cm is adequate for 92%, 12.8 cm for 98% and 14 cm for 100% of patients undergoing CCTA. Advances in knowledge: Reducing z-axis coverage in 320-detector CCTA can reduce DLP by approximately 27%.

Magnetic Resonance Imaging-Guided Spine Interventions.

MR imaging-guided interventions for treatment of low back pain and for diagnosis and treatment of soft tissue and bony spinal lesions have been shown to be feasible, effective, and safe. Advantages of this technique include the absence of ionizing radiation, the high tissue contrast, and multiplanar imaging options. Recent advancements in MR imaging systems allow improved image qualities and real-time guidance. One exciting application is MR imaging-guided cryotherapy of spinal lesions, including treating such lesions as benign osteoid osteomas and malignant metastatic disease in patients who are not good surgical candidates. This particular technique shows promise for local tumor control and pain relief in appropriate patients.

Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome.

We have previously shown that irritable bowel syndrome (IBS) patients have both visceral and cutaneous hyperalgesia. The neural mechanisms of these forms of hyperalgesia were further characterized by comparing cortical processing of both rectal distension (35, 55mmHg) and cutaneous heat nociceptive stimuli (foot immersion in 45 and 47 degrees C water bath) in IBS patients and in a group of healthy age/sex-matched controls. Our approach relied on functional magnetic resonance imaging neuroimaging analyses in which brain activation in age/sex-matched control subjects was subtracted from that found in IBS patients. These analyses revealed that both rectal distension and cutaneous heat stimuli evoked greater neural activity in several brain regions of IBS patients in comparison to age/sex-matched control subjects. These include those related to early stages of somatosensory processing (e.g. thalamus, somatosensory cortex) as well as those more related to cognitive and affective processing (insular, anterior cingulate, posterior cingulate, prefrontal cortex). Thus, our results support the hypothesis that hyperalgesia of IBS is manifested by increased somatosensory processing at all cortical levels. This was found to be the case not only for visceral hyperalgesia but also for cutaneous heat hyperalgesia, a likely form of secondary hyperalgesia. Furthermore, visceral and heat hyperalgesia were accompanied by increased neural activity within the same brain structures. These results support the hypothesis that visceral and cutaneous hyperalgesia in IBS patients is related to increased afferent processing in pathways ascending to the brain rather than to selectively increased activity at higher cortical levels (e.g. limbic and frontal cortical areas).

Magnetic resonance mapping of transplanted endothelial progenitor cells for therapeutic neovascularization in ischemic heart disease.

OBJECTIVE: Intramyocardial transplantation of endothelial progenitor cells (EPCs) has been previously correlated with significant augmentation of vascularity and improvement of left ventricular function following myocardial ischemia. However, precise intramyocardial localization of the transplanted cells and the extent of in situ cell migration are unknown. We present a novel technique using magnetic resonance imaging (MRI) to localize transplanted EPCs in ischemic hearts. METHODS: CD34-positive cells were isolated from human peripheral blood by magnetic bead selection: CD34-positive cells adhere to CD34-negative antibody coated magnetic beads, while CD34-negative cells do not. All cells were labeled with fluorescent DiI-dye for histological localization. CD34-positive cells or CD34-negative cells (105, 1 x 106 and 2 x 106 cells) were transplanted into non-ischemic (n = 6) or ischemic myocardium (n = 2) of Sprague-Dawley rats. Rats were sacrificed 24 h after cell transplantation. The resected hearts were imaged ex vivo using 3 and 8.5 T magnets. Morphological correlation between the MRI findings and fluorescent microscopy for identification of retained CD34-positive cells was evaluated. RESULTS: CD34-positive cells were identified as areas of low signal intensity on T2*-weighted images within the myocardium. These areas increased in size with the gradual increase in the echo time due to susceptibility effect. The extent of the low signal intensity at a given echo time was proportional to cell dosage. No areas of low signal were identified in the CD34-negative cell transplanted hearts. Histological localization of DiI-labeled CD34-positive cells documented a direct anatomic correlation with the localization of transplanted cells on the MRI images. CONCLUSIONS: Magnetically labeled EPCs transplanted for therapeutic neovascularization in myocardial ischemia can be visualized with ex vivo MRI at high-field strengths.

Myocyte injury along myofibers in left ventricular remodeling after myocardial infarction.

Left ventricular (LV) remodeling following myocardial infarction (MI) is considered to contribute to cardiac dysfunction. Though myofiber organization is a key component of cardiac structure, functional and anatomical features of injured myofiber during LV remodeling have not been fully defined. We investigated myocyte injury after acute MI in a mouse model. Mice were subjected to surgical coronary occlusion/reperfusion by left anterior descending coronary artery (LAD) ligation and examined at 1 week and 4 weeks post-MI. Magnetic resonance imaging (MRI) analysis demonstrated a significant decrease in systolic regional wall thickening (WT) in the border and remote zones at 4 weeks post-MI compared to that at 1 week post-MI (-86% in border zone, P<0.05, and -77% in remote zone, P<0.05). Histological assays demonstrated that a broad fibrotic scar extended from the initial infarct zone to the remote zone along mid-circumferential myofibers. Of particular note was the fact that no fibrosis was found in longitudinal myofibers in the epi- and endo-myocardium. This pattern of the scar formation coincided with the helical ventricular myocardial band (HVMB) model, introduced by Torrent-Guasp. MRI analysis demonstrated that the extension of the fibrotic scar along the band might account for the progression in cardiac dysfunction during LV remodeling.

VEGF and TGF-beta are required for the maintenance of the choroid plexus and ependyma.

Although the role of vascular endothelial growth factor (VEGF) in developmental and pathological angiogenesis is well established, its function in the adult is less clear. Similarly, although transforming growth factor (TGF) beta is involved in angiogenesis, presumably by mediating capillary (endothelial cell [EC]) stability, its involvement in quiescent vasculature is virtually uninvestigated. Given the neurological findings in patients treated with VEGF-neutralizing therapy (bevacizumab) and in patients with severe preeclampsia, which is mediated by soluble VEGF receptor 1/soluble Fms-like tyrosine kinase receptor 1 and soluble endoglin, a TGF-beta signaling inhibitor, we investigated the roles of VEGF and TGF-beta in choroid plexus (CP) integrity and function in adult mice. Receptors for VEGF and TGF-beta were detected in adult CP, as well as on ependymal cells. Inhibition of VEGF led to decreased CP vascular perfusion, which was associated with fibrin deposition. Simultaneous blockade of VEGF and TGF-beta resulted in the loss of fenestrae on CP vasculature and thickening of the otherwise attenuated capillary endothelium, as well as the disappearance of ependymal cell microvilli and the development of periventricular edema. These results provide compelling evidence that both VEGF and TGF-beta are involved in the regulation of EC stability, ependymal cell function, and periventricular permeability.

In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction.

The therapeutic potential of administering stem cells to promote angiogenesis and myocardial tissue regeneration after infarction has recently been demonstrated. Given the advantages of using embryonic stem cells and mouse models of myocardial infarction for furthering the development of this therapeutic approach, the purpose of this study was to determine if embryonic stem cells could be loaded with superparamagnetic iron oxide (SPIO) particles and imaged in a mouse model of myocardial infarction over time using MRI. Mouse embryonic stem cells were labeled with SPIO particles. When incubated with 11.2, 22.4, and 44.8 microg Fe/ml of SPIO particles, cells took up increasing amounts of iron oxide. Embryonic stem cells loaded with SPIO compared to unlabeled cells had similar viability and proliferation profiles for up to 14 days. Free SPIO injected into infarcted myocardium was not observable within 12 hr after injection. After injection of three 10-microl aliquots of 10(7) SPIO-loaded cells/ml into infarcted myocardium, MRI demonstrated that the mouse embryonic stem cells were observable and could be seen for at least 5 weeks after injection. These findings support the ability of MRI to test the long-term therapeutic potential of embryonic stem cells in small animals in the setting of myocardial infarction.

Processing words with emotional connotation: an FMRI study of time course and laterality in rostral frontal and retrosplenial cortices.

Responses of rostral frontal and retrosplenial cortices to the emotional significance of words were measured using functional magnetic resonance imaging (fMRI). Twenty-six strongly right-handed participants engaged in a language task that alternated between silent word generation to categories with positive, negative, or neutral emotional connotation and a baseline task of silent repetition of emotionally neutral words. Activation uniquely associated with word generation to categories with positive or negative versus neutral emotional connotation occurred bilaterally in rostral frontal and retrosplenial cortices. Furthermore, the time courses of activity in these areas differed, indicating that they subserve different functions in processing the emotional connotation of words. Namely, the retrosplenial cortex appears to be involved in evaluating the emotional salience of information from external sources, whereas the rostral frontal cortex also plays a role in internal generation of words with emotional connotation. In both areas, activity associated with positive or negative emotional connotation was more extensive in the left hemisphere than the right, regardless of valence, presumably due to the language demands of word generation. The present findings localize specific areas in the brain that are involved in processing emotional meaning of words within the brain's distributed semantic system. In addition, time course analysis reveals diverging mechanisms in anterior and posterior cortical areas during processing of words with emotional significance.

A pneumatic vibrotactile stimulation device for fMRI.

Mapping the functional response of the somatosensory cortex is useful both for characterizing normal brain activity and for determining the functional integrity of damaged cortex compromised by stroke or other neurological insults. A variety of stimulators have been used to produce somatosensory cortex activation in functional brain imaging, including brushes and swabs operated manually, pneumatically and mechanically powered mechanical vibrators, air puffs, and vibrating ceramic piezoelectric wafers and benders. A closed-system, pneumatically driven rubber diaphragm is reported that overcomes many of the limitations of existing vibrotactile devices and produces robust sensory cortex activation in an fMRI experiment.