Design and fabrication of prototype piezoelectric adjustable X-ray mirrors.

Lynx, a next generation X-ray observatory concept currently under study, requires lightweight, high spatial resolution X-ray mirrors. Here we detail the development and fabrication of one of the candidate technologies for Lynx, piezoelectric adjustable X-ray optics. These X-ray mirrors are thin glass shell mirrors with Cr/Ir X-ray reflective coatings on the mirror side and piezoelectric thin film actuators on the actuator side. Magnetron sputtering was used to deposit metal electrodes and metal-oxide piezoelectric layers. The piezoelectric (Pb0.995(Zr0.52Ti0.48)0.99Nb0.01O3) was divided into 112 independent piezoelectric actuators, with 100% yield achieved. We discuss the fabrication procedure, residual thermal stresses and tuning of the Cr/Ir coating stress for the purposes of stress balancing.

Leptomeningeal Enhancement on 3D-FLAIR MRI in Multiple Sclerosis: Systematic Observations in Clinical Practice.

BACKGROUND AND PURPOSE: Meningeal inflammation is implicated in cortical demyelination and disability progression in multiple sclerosis (MS). Gadolinium (Gd)-enhanced 3-dimensional (3D) FLAIR (fluid-attenuated inversion recovery) magnetic resonance imaging (MRI) can identify leptomeningeal enhancement (LME) in MS. Further characterization is needed to determine if LME is an imaging biomarker for meningeal inflammation. We sought to characterize the natural history of LME in the community setting, including persistence/resolution, effect of disease-modifying therapy, scanner variability, timing of acquisition, and imaging pitfalls that may lead to misinterpretation. METHODS: A total of 341 MRI exams with Gd-enhanced 3D-FLAIR were reviewed in MS and non-MS patients to determine frequency of enhancement by MS subtype and association with therapy. A phantom was used to assess scanner variability. Two MS patients with seven LME were imaged at four postinjection time points to generate time-intensity curves. Imaging pitfalls were compiled. RESULTS: A total of 16.6% (40/241) of MS patients revealed LME compared to 8% (8/100) in non-MS patients (P = .04). There was no association with MS subtype, therapy, or disease activity. Detection using General Electric's version of 3D-FLAIR (29%) was greater than with Siemen's 3D-FLAIR (12%) at 1.5T (Tesla) (P < .001). Lesions were generally stable but resolved in 2 patients following high-dose steroids. LME kinetics were heterogeneous, even within patients, without uniform optimal time for acquisition. Enhancement curves exhibited three different variations, similar to the two-compartment model. Imaging pitfalls included enhancements of uncertain biologic significance, cortical veins and anatomic structures, and imaging artifacts. CONCLUSIONS: Awareness of LME characteristics, variability with imaging parameters, and imaging pitfalls will facilitate determining the potential role as an imaging biomarker for meningeal inflammation.

Bilateral aortic origins of the vertebral arteries with right vertebral artery arising distal to left subclavian artery: case report.

BACKGROUND: Bilateral aortic origins of the vertebral arteries are a rare anatomic variant, with fewer than 20 cases reported in the literature. This particular variant has only been reported twice. CASE DESCRIPTION: A 35-year-old woman presented to the emergency department after trauma to the head and a witnessed convulsion. Subsequent workup included MRI/MRA, which resulted in identification of the anomaly. CONCLUSION: The clinical importance of aortic arch anomalies lies in that it may be a source of misinterpretation, as one may conclude occlusion of the vertebral artery if the aberrant origin is not included in the MRA or CTA imaging parameters. Therefore, it is important to scan through the entire aortic arch to just below the level of the ligamentum arteriosum when performing these noninvasive modalities. In addition, vertebral arteries arising from the aortic arch have an increased risk of dissection.

Spinal cord diffusion tensor imaging and fiber tracking can identify white matter tract disruption and glial scar orientation following lateral funiculotomy.

Diffusion tensor magnetic resonance imaging (DTI) provides data concerning water diffusion in the spinal cord, from which white matter tracts may be inferred, and connectivity between spinal cord segments may be determined. We evaluated this potential application by imaging spinal cords from normal adult rats and rats that received cervical lateral funiculotomies, disrupting the rubrospinal tract (RST). Vitrogen and fibroblasts were transplanted into the surgical lesion at time of injury in order to fill the cavity. At 10 weeks, animals were sacrificed; the spinal cords were dissected out and then imaged in a 9.4-Tesla magnet. DTI tractography demonstrated the disruption of the rubrospinal tract axons while indicating which axon tracts were preserved. Additionally, DTI imaging could identify the orientation of glial processes in the gray matter adjacent to the site of injury. In the injured animals, reactive astrocytes in adjacent gray matter appeared to orient themselves perpendicular to white matter tracts. In summary, DTI identified not only white matter disruption following injury, but could distinguish the orientation of the accompanying glial scar.

MRI diffusion coefficients in spinal cord correlate with axon morphometry.

Following spinal cord injury, diffusion MRI (DWI) has been shown to detect injury and functionally significant neuroprotection following treatment that otherwise would go undetected with conventional MRI. The underlying histologic correlates to directional apparent diffusion coefficients (ADC) obtained with DWI have not been determined, however, and we address this issue by directly correlating ADC values with corresponding axon morphometry in the normal rat cervical spinal cord. ADC values transverse (perpendicular) and longitudinal (parallel) to axons both correlate with axon counts, however each directional ADC reflects distinct histologic parameters. DWI may therefore be capable of providing specific histologic data regarding the integrity of white matter.

Ex vivo evaluation of ADC values within spinal cord white matter tracts.

BACKGROUND AND PURPOSE: Our purpose was to evaluate the effect of fixative on apparent diffusion coefficient (ADC) values and anisotropy within spinal cord white matter. As glutaraldehyde (GL) better preserves axonal ultrastructure as compared with paraformaldehyde (PF), we hypothesize that spinal cord white matter fixed with GL will have increased anisotropic water diffusion as compared with specimens fixed with PF. METHODS: Eleven rats were perfusion-fixed with either 4% PF or a combination of 2.5% GL and 4% PF. Diffusion-weighted imaging of the ex vivo spinal cord was performed using a 9.4T magnet with b values up to 3100 s/mm(2). In-plane resolution was 39 mum x 39 mum, and section thickness was 500 mum. RESULTS: Overall, animals fixed with a combination of GL and PF (GL-PF) showed a greater increase in longitudinal ADC (lADC) as compared to those fixed with PF only, without differences in transverse ADC (tADC). As a consequence of the increased lADC, overall anisotropic diffusion increased in those animals fixed with GL-PF, as measured with an anisotropy index (AI = tADC/lADC). Evaluation of specific tracts demonstrated that lADC for animals fixed with GL-PF were significantly elevated in the rubrospinal, vestibulospinal, and reticulospinal tracts as compared with animals fixed with PF only. CONCLUSION: Using a fixative of GL-PL results in increased anisotropy (decreased AI values) in spinal cord white matter tracts, as compared with PF fixation only, largely owing to increases in the lADC values. This finding may be due to better fixation of intra-axonal cytoskeletal proteins that results when GL is combined with PF and sheds further light on underlying sources of anisotropic water diffusion in CNS white matter.

Apparent diffusion coefficients in spinal cord transplants and surrounding white matter correlate with degree of axonal dieback after injury in rats.

BACKGROUND AND PURPOSE: Abnormal apparent diffusion coefficient (ADC) values in injured spinal cord white matter and fibroblast transplants have been shown to correspond with qualitative histologic findings of axonal loss or regeneration. We proposed that ADC values would correlate with quantitative axonal tracing in the transected rubrospinal tract (RST). METHODS: Eleven rats received right-sided lateral funiculus lesions at C3-4 (disrupting the RST) and transplantation of fibroblasts that were unmodified or modified to secrete brain-derived neurotrophic factor (BDNF). Behavioral tests measured hindlimb function at 1, 2, 4, 6, 8, 10, and 12 weeks after injury. At 12 weeks after injury, the antegrade axon tracer biotinylated dextran amine was stereotactically injected into the red nucleus to label the injured RST axons. Animals were sacrificed 2 weeks later. Diffusion-weighted MR imaging of the excised, fixed spinal cord specimens was then performed at 9.4 T. RESULTS: In white matter surrounding transplants, ADC values transverse to axons were elevated and ADC values longitudinal to axons were decreased. These ADC values were more abnormal closer to the transplant, and this correlated with decreases in numbers of labeled RST axons. ADC values in BDNF-expressing fibroblast transplants were significantly lower than those in unmodified fibroblast transplants, and these lower values correlated with decreased axonal dieback. Behaviorally, all animals showed partial recovery, but animals with BDNF-expressing fibroblast transplants had slightly improved hindlimb function compared to those with unmodified fibroblast transplants. CONCLUSION: ADC values may be able to evaluate graft function after spinal cord injury by demonstrating the degree of axonal dieback and preservation.

Distinguishing ischemic stroke from the stroke-like lesions of MELAS using apparent diffusion coefficient mapping.

We report two patients with migraine, acute visual field defects and other neurological symptoms who were found to have high T(2) signal and FLAIR abnormalities on brain MRI in temporal and parieto-occipital regions. In these patients, the apparent diffusion coefficient (ADC) of their lesions was increased, distinguishing these lesions from those of ischemic stroke. Both were ultimately diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). We conclude that conventional MRI when used with diffusion-weighted MR imaging may be invaluable in detecting mitochondrial-related CNS dysfunction.

Diffusion-weighted imaging of the spinal cord.

Spinal cord DWI may be useful in providing information not available with conventional MR imaging. More work, however, is required to explain what the qualitative and quantitative results actually represent. Computer simulations and detailed radiologic-histologic correlations will therefore be necessary.

Complete regression of intracranial arteriovenous malformations.

BACKGROUND: Spontaneous and complete regression of intracranial arteriovenous malformations (AVMs) is a rare occurrence, with only 59 angiographically proven cases reported in the English literature. We present three new cases and perform a literature review to determine possible mechanisms underlying this unusual phenomenon. METHODS: Three patients with angiographically proven AVMs demonstrated complete obliteration of the AVM on follow-up angiography. Two patients had MRIs performed at the time of follow-up angiography. RESULTS: A literature review of all reported cases shows that the vast majority (88%) of spontaneously closing AVMs had a single draining vein as did our three cases. In addition, hemodynamic alterations of intracranial (IC) blood flow, including intracranial hemorrhage, were seen in a majority (79%) of patients, including two of our three cases. MRI was performed in two of our three cases and showed a thrombosed-draining vein in both. CONCLUSIONS: Complete spontaneous regression of intracranial AVMs is a rare occurrence. The phenomenon seems to require the interaction of hemodynamic changes in compromising or closing the limited, usually single, venous drainage pathway from the AVM. Hemorrhage may contribute to the effect by further compromising flow though the lesion, or it may merely be a phenomenon associated with the effects of venous hypertension on the AVM nidus.

Indirect measurement of regional axon diameter in excised mouse spinal cord with q-space imaging: simulation and experimental studies.

Q-space imaging (QSI), a diffusion MRI technique, can provide quantitative tissue architecture information at cellular dimensions not amenable by conventional diffusion MRI. By exploiting regularities in molecular diffusion barriers, QSI can estimate the average barrier spacing such as the mean axon diameter in white matter (WM). In this work, we performed ex vivo QSI on cervical spinal cord sections from healthy C57BL/6 mice at 400 MHz using a custom-designed uniaxial 50T/m gradient probe delivering a 0.6 microm displacement resolution capable of measuring axon diameters on the scale of 1 microm. After generating QSI-derived axon diameter maps, diameters were calculated using histology from seven WM tracts (dorsal corticospinal, gracilis, cuneatus, rubrospinal, spinothalamic, reticulospinal, and vestibulospinal tracts) each with different axon diameters. We found QSI-derived diameters from regions drawn in the seven WM tracts (1.1 to 2.1 microm) to be highly correlated (r(2)=0.95) with those calculated from histology (0.8 to 1.8 microm). The QSI-derived values overestimated those obtained by histology by approximately 20%, which is likely due to the presence of extra-cellular signal. Finally, simulations on images of synthetic circular axons and axons from histology suggest that QSI-derived diameters are informative despite diameter and axon shape variation and the presence of intra-cellular and extra-cellular signal. QSI may be able to quantify nondestructively changes in WM axon architecture due to pathology or injury at the cellular level.

Hemostatic and neuroprotective effects of human recombinant activated factor VII therapy after traumatic brain injury in pigs.

Human recombinant activated factor-VII (rFVIIa) has been used successfully in the treatment of spontaneous intracerebral hemorrhage. In addition, there is increasing interest in its use to treat uncontrolled bleeding of other origins, including trauma. The aim of this study was to evaluate the safety and potential effectiveness of rFVIIa to mitigate bleeding using a clinically relevant model of traumatic brain injury (TBI) in the pig. A double injury model was chosen consisting of (1) an expanding cerebral contusion induced by the application of negative pressure to the exposed cortical surface and (2) a rapid rotational acceleration of the head to induce diffuse axonal injury (DAI). Injuries were performed on 10 anesthetized pigs. Five minutes after injury, 720 microg/kg rFVIIa (n=5) or vehicle control (n=5) was administered intravenously. Magnetic resonance imaging (MRI) studies were performed within 30 min and at 3 days post-TBI to determine the temporal expansion of the cerebral contusion. Euthanasia and histopathologic analysis were performed at day 3. This included observations for hippocampal neuronal degeneration, axonal pathology and microclot formation. The expansion of contusion volume over the 3 days post-injury period was reduced significantly in animals treated with rFVIIa compared to vehicle controls. Surprisingly, immunohistochemical analysis demonstrated that the number of dead/dying hippocampal neurons and axonal pathology was reduced substantially by rFVIIa treatment compared to vehicle. In addition, there was no difference in the extent of microthrombi between groups. rFVIIa treatment after TBI in the pig reduced expansion of hemorrhagic cerebral contusion volume without exacerbating the severity of microclot formation. Finally, rFVIIa treatment provided a surprising neuroprotective effect by reducing hippocampal neuron degeneration as well as the extent of DAI.

The impact of methylprednisolone on lesion severity following spinal cord injury.

STUDY DESIGN: Retrospective study comparing spinal cord injury (SCI) lesion characteristics in methylprednisolone (MPS) treated versus untreated patients as demonstrated by magnetic resonance (MR) imaging. OBJECTIVE: Determine if the administration of MPS immediately following SCI affects lesion severity. SUMMARY OF BACKGROUND DATA: The administration of MPS in the setting of acute SCI has become controversial. Since magnetic resonance imaging (MRI) is sensitive for the detection of spinal cord edema and hemorrhage, changes in lesion characteristics would support a biologic effect due to MPS. METHODS: Patients with cervical spinal injury treated with the recommended dose of methylprednisolone (bolus 30 mg/kg + 5.4 mg/kg per hour over 24 hours) initiated within 8 hours of injury were compared to historical controls that did not receive steroids. All patients (n = 82) sustained clinically complete SCI (ASIA Grade A) and underwent MRI on the same 1.5 Tesla unit. The length of spinal cord edema, presence/absence of intramedullary hemorrhage, and length of intramedullary hemorrhage were measured on T2-weighted and gradient echo MR images. Comparisons of lesion severity were then made between untreated and treated subjects. RESULTS: Forty-eight of 82 patients with complete injuries received MPS therapy. After accounting for differences in the mean age of the treatment and control groups, multiple regression analysis demonstrated a persistent reduction in the mean length of intramedullary hemorrhage, 2.6 U in the treatment group versus 4.4 U in the control group (P = 0.04). Although there was a reduction in the number of patients exhibiting spinal cord hemorrhage in the treated group compared with the untreated group (65% vs. 91%), this result was not statistically significant (P = 0.16). There was no statistically significant effect of MPS treatment on the mean length of the spinal cord edema between treated versus untreated subjects (10.3 vs. 12.0, respectively, P = 0.85). CONCLUSIONS: MRI suggests MPS therapy in the acute phase of spinal cord injury may decrease the extent of intramedullary spinal cord hemorrhage.

In vivo DTI evaluation of white matter tracts in rat spinal cord.

PURPOSE: To determine whether differences in specific spinal cord white matter (WM) tracts can be detected with in vivo DTI. MATERIALS AND METHODS: In vivo DTI was performed on six rats at the lower thoracic region using a 4.7T magnet. Axial diffusion images were obtained with diffusion gradients applied in six independent directions, with low and high b-values equal to 0 and 692 seconds/mm(2), respectively. Regions of interest (ROIs) were selected corresponding to the major spinal cord tracts, including the dorsal cortical spinal tract (dCST), fasciculus gracilis (FG), rubrospinal tract (RST), vestibulospinal tract (VST), and reticulospinal tract (ReST). RESULTS: ANOVA demonstrated overall differences between tracts for all of the DTI parameters, including fractional anisotropy (FA), trace diffusion (Tr), longitudinal diffusivity (EL = lambda(1)), and transverse diffusivity (ET = (lambda(2) + lambda(3))/2). Similarly to previous ex vivo analyses, the spinal cord tract with the largest and most widely spaced axons (VST) had the largest EL and ET. CONCLUSION: The principal diffusivities appear to reflect axon morphologic differences between the WM tracts that are not as well appreciated with FA and Tr.

Diffusion-weighted MRI and the evaluation of spinal cord axonal integrity following injury and treatment.

Diffusion-based magnetic resonance imaging (MRI) (DWI) has been shown experimentally to detect both injury and functionally significant neuroprotection of injured spinal cord white matter that would otherwise go undetected with conventional MRI techniques. The diffusion of water in the central nervous system (CNS) is thought to be affected by both its location (intracellular or extracellular), and by diffusion barriers formed by cell membranes and myelin sheaths. There is, however, controversy concerning how to obtain, interpret, and present DWI data. Computer simulations and MR microscopy have been helpful in resolving some of these issues, as well as determining exact histologic correlates to DWI findings.

Ex vivo MR determined apparent diffusion coefficients correlate with motor recovery mediated by intraspinal transplants of fibroblasts genetically modified to express BDNF.

The purpose of this study was to determine whether apparent diffusion coefficients (ADCs) in ex vivo spinal cord white matter, calculated from diffusion weighted MR (DWI) images, correlate with axonal growth and behavioral recovery following subtotal hemisection and transplantation of fibroblasts genetically modified to express brain derived neurotrophic factor (BDNF). These genetically modified fibroblasts have been shown to promote axonal growth, diminish retrograde degenerative changes in axotomized Red nucleus neurons, and are associated with behavioral recovery. Since changes in ADC appear to reflect damage to axons and myelin sheaths, which conventional MR techniques do not identify, partial repair mediated by BDNF-secreting fibroblasts should be detected with ADC measures. Accordingly, we transplanted unmodified fibroblasts (Fb-UM) or fibroblasts modified to secrete BDNF (Fb-BDNF) into cervical subtotal hemisection cavities in adult rats. Rats with Fb-BDNF transplants showed significantly greater behavioral recovery over 12 weeks, as measured by tests of forelimb exploration and open field locomotor activity. Lesion sizes and transplant survival did not differ between the two groups, but immunocytochemical examination showed substantial growth of axons into the Fb-BDNF grafts and little growth into the Fb-UM grafts. Fixed spinal cords were imaged in a 9.4-T magnet. ADCs perpendicular (tADC) and parallel (lADC) to the long axis of the cord were measured in the dorsal lateral white matter, rostral and caudal to the transplant. tADC values and anisotropy index (AI = tADC/lADC) were elevated in both transplant types, indicating white matter damage, but were closer to normal in rats with Fb-BDNF, consistent with known neuroprotection and axonal growth elicited by BDNF. Closer to normal tADC and AI values correlated with improved behavioral recovery. These findings suggest that high-resolution imaging with measurement of tADC and lADC can provide a measure of functionally significant repair that may otherwise go undetected with conventional MR techniques.

Vertebrobasilar thrombolysis with intravenous tirofiban: case report.

The use of thrombolytic agents in the setting of established cerebral infarction is limited by concerns for hemorrhagic transformation. Novel thrombolytic approaches, which have received minimal consideration, may be associated with lower risks of hemorrhage. We illustrate vertebrobasilar thrombolysis with intravenous tirofiban, a selective platelet glycoprotein IIb/IIIa receptor antagonist, and discuss the potential thrombolytic properties of this class of antithrombotics.

Assessment of axonal fiber tract architecture in excised rat spinal cord by localized NMR q-space imaging: simulations and experimental studies.

NMR q-space imaging is a method designed to obtain information from porous materials where diffusion-diffraction phenomena were observed from which pore size was derived. Recently, the technique has been applied to the study of biological structures as well. Although diffusive diffraction has so far not been observed in multicellular systems, displacement profiles have been used with some success as a means to estimate structure size. However, there have been no quantitative correlations of the retrieved structure sizes with histology. Clearly, the complexity of tissue architecture poses significant challenges to the interpretation of q-space data. In this work, simulations were first performed on a two-compartment model to demonstrate the effects of interference of the diffraction patterns arising from intra and extra-axonal compartments and finite boundary permeability on q-space data. Second, q-space echo attenuation was simulated on the basis of histologic images of various rat spinal cord fiber tracts and the information obtained from the displacement profiles were compared with structural parameters computed from the histologic images. The results show that calculated mean displacements and kurtosis parallel mean axon size and axonal density. Finally, spatially localized q-space measurements were carried out at the locations where simulations had previously been performed, resulting in displacement data that support those obtained by simulation. The data suggest the NMR q-space approach has potential for nondestructive analysis of the axonal architecture in the mammalian spinal cord.