Spinal cord imaging markers and recovery of standing with epidural stimulation in individuals with clinically motor complete spinal cord injury.

Spinal cord epidural stimulation (scES) is an intervention to restore motor function in those with severe spinal cord injury (SCI). Spinal cord lesion characteristics assessed via magnetic resonance imaging (MRI) may contribute to understand motor recovery. This study assessed relationships between standing ability with scES and spared spinal cord tissue characteristics at the lesion site. We hypothesized that the amount of lateral spared cord tissue would be related to independent extension in the ipsilateral lower limb. Eleven individuals with chronic, clinically motor complete SCI underwent spinal cord MRI, and were subsequently implanted with scES. Standing ability and lower limb activation patterns were assessed during an overground standing experiment with scES. This assessment occurred prior to any activity-based intervention with scES. Lesion hyperintensity was segmented from T2 axial images, and template-based analysis was used to estimate spared tissue in anterior, posterior, right, and left spinal cord regions. Regression analysis was used to assess relationships between imaging and standing outcomes. Total volume of spared tissue was related to left (p = 0.007), right (p = 0.005), and bilateral (p = 0.011) lower limb extension. Spared tissue in the left cord region was related to left lower limb extension (p = 0.019). A positive trend (p = 0.138) was also observed between right spared cord tissue and right lower limb extension. In this study, MRI measures of spared spinal cord tissue were significantly related to standing outcomes with scES. These preliminary results warrant future investigation of roles of supraspinal input and MRI-detected spared spinal cord tissue on lower limb motor responsiveness to scES.

The relationships among spinal CSF flows, spinal cord geometry, and vascular correlations: evidence of intrathecal sources and sinks.

We studied relationships of cerebral spinal fluid (CSF) pulsatile flow at cervical, thoracic, and lumbar levels using phase-contrast cine MRI (PCCMRI) to determine the following: 1) instantaneous and average net flows at cervical, thoracic, and lumbar levels, 2) stochastic correlations of CSF flow with major arterial supplies and major draining veins, and 3) whether adjustments of cord-flow curves-using cord cross-sectional areas, caudal lengths, and caudal volumes-would normalize flow curves from different levels. We scanned 15 healthy volunteers without anesthesia, ages 23-46 yr, using external, retrocardiac-gated, two-dimensional PCCMRI at 3T. Transverse scans of the subarachnoid space, arteries, and veins were acquired and analyzed at cervical, thoracic, and lumbar levels. Instantaneous CSF flow decreased craniocaudally along the full time course of a cardiac cycle. Downward net flow generally increased craniocaudally. During diastole, instantaneous CSF flow decreased proportionally to cross-sectional area, caudal residual length, and caudal residual volume of the cord. The proportionalities were less consistent during systole. CSF, internal carotid artery (ICA), vertebral artery, and lower aorta temporal correlations were highest in systole and decreased craniocaudally. CSF flow temporally correlated better with lower aorta flow than with the ICA at T7 and L2 during systole but not diastole. Inferior vena cava temporal correlation increased craniocaudally. We conclude that whereas instantaneous flow is attenuated cranial caudally, net downward flow, per cardiac cycle, increases caudally, becoming statistically significant at T7 and below the conus medullaris. We can explain the results with the assumption of cord CSF production and peripheral-dominated CSF absorption.

Multi-Site Spinal Cord Transcutaneous Stimulation Facilitates Upper Limb Sensory and Motor Recovery in Severe Cervical Spinal Cord Injury: A Case Study.

Individuals with cervical spinal cord injury (SCI) rank regaining arm and hand function as their top rehabilitation priority post-injury. Cervical spinal cord transcutaneous stimulation (scTS) combined with activity-based recovery training (ABRT) is known to effectively facilitate upper extremity sensorimotor recovery in individuals with residual arm and hand function post SCI. However, scTS effectiveness in facilitating upper extremity recovery in individuals with severe SCI with minimal to no sensory and motor preservation below injury level remains largely unknown. We herein introduced a multimodal neuro-rehabilitative approach involving scTS targeting systematically identified various spinal segments combined with ABRT. We hypothesized that multi-site scTS combined with ABRT will effectively neuromodulate the spinal networks, resulting in improved integration of ascending and descending neural information required for sensory and motor recovery in individuals with severe cervical SCI. To test the hypothesis, a 53-year-old male (C2, AIS A, 8 years post-injury) received 60 ABRT sessions combined with continuous multi-site scTS. Post-training assessments revealed improved activation of previously paralyzed upper extremity muscles and sensory improvements over the dorsal and volar aspects of the hand. Most likely, altered spinal cord excitability and improved muscle activation and sensations resulted in observed sensorimotor recovery. However, despite promising neurophysiological evidence pertaining to motor re-activation, we did not observe visually appreciable functional recovery on obtained upper extremity motor assessments.

Predictive values of spinal cord diffusion magnetic resonance imaging to characterize outcomes after contusion injury.

OBJECTIVES: To explore filtered diffusion-weighted imaging (fDWI), in comparison with conventional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), as a predictor for long-term locomotor and urodynamic (UD) outcomes in Yucatan minipig model of spinal cord injury (SCI). Additionally, electrical conductivity of neural tissue using D-waves above and below the injury was measured to assess correlations between fDWI and D-waves data. METHODS: Eleven minipigs with contusion SCI at T8-T10 level underwent MRI at 3T 4 h. post-SCI. Parameters extracted from region of interest analysis included Daxial from fDWI at injury site, fractional anisotropy and radial diffusivity from DTI above the injury site along with measures of edema length and cord width at injury site from T2 -weighted images. Locomotor recovery was assessed pre- and weekly post-SCI through porcine thoracic injury behavior scale (PTIBS) and UD were performed pre- and at 12 weeks of SCI. D-waves latency and amplitude differences were recorded before and immediately after SCI. RESULTS: Two groups of pigs were found based on the PTIBS at week 12 (p < 0.0001) post-SCI and were labeled "poor" and "good" recovery. D-waves amplitude decreased below injury and increased above injury. UD outcomes pre/post SCI changed significantly. Conventional MRI metrics from T2 -weighted images were significantly correlated with diffusion MRI metrics. Daxial at injury epicenter was diminished by over 50% shortly after SCI, and it differentiated between good and poor locomotor recovery and UD outcomes. INTERPRETATION: Similar to small animal studies, fDWI from acute imaging after SCI is a promising predictor for functional outcomes in large animals.

Recognizing false ischemic penumbras in CT brain perfusion studies.

Computed tomography (CT) plays a pivotal role in the diagnosis of acute stroke and in treatment decision making. CT perfusion imaging performed with intravenous iodinated contrast material allows calculation of the time to peak enhancement, mean transit time, and cerebral blood volume, important parameters for differentiating between an ischemic penumbra, which might benefit from intravascular therapy with thrombolytic agents, and infarcted tissue, which would not benefit from such therapy. Differentiation between the two entities is important because thrombolytic therapy is associated with an increased risk for intracranial hemorrhage. A finding of delay in peak enhancement or increased mean transit time in a region with normal or only slightly abnormal cerebral blood volume is suggestive of an ischemic penumbra; however, accurate interpretation of the CT perfusion parameters may be difficult in the presence of a cerebrovascular anatomic variant or physiologic condition that produces benign oligemia leading to a false appearance of penumbra. For this reason, CT perfusion parameters must be correlated with the clinical history and findings at unenhanced head CT, angiography or CT angiography, and diffusion-weighted magnetic resonance imaging. The authors identify five possible causes of false penumbras, each of which produces a different pattern at imaging: upstream flow restriction, evolution of ischemic change, vascular dysregulation, positioning of the patient's head at an angle during image acquisition, and variant anatomy in the circle of Willis. Familiarity with the imaging patterns and causes of false penumbras may increase the radiologist's confidence in diagnosis and help avoid costly errors in treatment.

ECG Gating Is More Precise Than Peripheral Pulse Gating When Quantifying Spinal CSF Pulsations Using Phase Contrast Cine MRI.

PURPOSE: To compare accuracy of spinal cerebrospinal fluid (CSF) pulsatile flow measurements at cervical, thoracic, and lumbar levels using Phase Contrast Cine MRI (PCCMRI) with retrospective electrocardiogram (recg) vs. retrospective peripheral pulse gating (rppg) gating. METHODS: We scanned 10 healthy volunteers, ages 23-46 years, using external recg-gated or rppg-gated 2D PCCCMRI at 3T. Transverse scans of CSF, arteries and veins scans were at C1/C4/T1/T7/L1-L3. Data were analyzed with custom Matlab-based software, measuring CSF, arterial (descending aorta, abdominal aorta, common carotid artery, ICA, and vertebral artery) and venous (internal jugular vein and inferior vena cava) flow, velocity and region of interest area. RESULTS: recgPCCMRI produced less quantitative and temporal statistical variation than pcgPCCMRI when analyzing CSF flow. The instantaneous recgPCCMRI CSF flows consistently decreased craniocaudally, while the results with rppgPCCMRI were less consistent. The recgPCCMRI root mean square error values were 6.04, 6.94, 4.81, 4.49, and 4.16 for C1, C4, T1, T7, and L2, compared with 7.24, 8.97, 7.9, 7.82, and 6.68 for rppgPCCMRI. Results were independent of analysts. Summations of standard errors produced similar results. RppgPCCMRI also showed increase variability of CSF flow correlations with arteries and veins compared to recgPCCMRI. None-the-less, when recgPCCMRI is considered the reference standard, there is good correlations between rppgPCCMRI and recgPCCMRIdata sets, when averaged over cohorts of at least five subjects. CONCLUSION: Our results indicated that recgPCCMRI is more quantitatively and temporally precise than rppgPCCMRI in CSF quantitative flow analysis. Pulse-gating CSF flow results are reasonable when averaged over cohorts of at least five subjects, but subtle conclusions should be interpreted with caution.

Spinal Cord Imaging Markers and Recovery of Volitional Leg Movement With Spinal Cord Epidural Stimulation in Individuals With Clinically Motor Complete Spinal Cord Injury.

Previous studies have shown that epidural stimulation of the lumbosacral spinal cord (scES) can re-enable lower limb volitional motor control in individuals with chronic, clinically motor complete spinal cord injury (SCI). This observation entails that residual supraspinal connectivity to the lumbosacral spinal circuitry still persisted after SCI, although it was non-detectable when scES was not provided. In the present study, we aimed at exploring further the mechanisms underlying scES-promoted recovery of volitional lower limb motor control by investigating neuroimaging markers at the spinal cord lesion site via magnetic resonance imaging (MRI). Spinal cord MRI was collected prior to epidural stimulator implantation in 13 individuals with chronic, clinically motor complete SCI, and the spared tissue of specific regions of the spinal cord (anterior, posterior, right, left, and total cord) was assessed. After epidural stimulator implantation, and prior to any training, volitional motor control was evaluated during left and right lower limb flexion and ankle dorsiflexion attempts. The ability to generate force exertion and movement was not correlated to any neuroimaging marker. On the other hand, spared tissue of specific cord regions significantly and importantly correlated with some aspects of motor control that include activation amplitude of antagonist (negative correlation) muscles during left ankle dorsiflexion, and electromyographic coordination patterns during right lower limb flexion. The fact that amount and location of spared spinal cord tissue at the lesion site were not related to the ability to generate volitional lower limb movements may suggest that supraspinal inputs through spared spinal cord regions that differ across individuals can result in the generation of lower limb volitional motor output prior to any training when epidural stimulation is provided.

Demonstration of an anterior diffusional pathway for solutes in the normal human eye with high spatial resolution contrast-enhanced dynamic MR imaging.

PURPOSE: The present studies were conducted to determine whether a diffusional pathway for solutes exists from the ciliary body stroma to the anterior chamber of the human eye. The existence of such a pathway has been demonstrated in rabbits and monkeys, but such a pathway in humans would necessitate a shift in the physiological paradigm of the blood-aqueous barrier. METHODS: Seven normal human volunteers (five men, two women; age range, 27 to 59 years) underwent nine dynamic T1-weighted, spin-echo MR imaging studies, using intravenous, gadolinium-based contrast agents. RESULTS: In all cases, signal intensity rose rapidly in the ciliary body. In all subjects, there was a measurable latent rise in signal strength (enhancement) in the anterior chamber. Signal enhancement typically occurred in the angle of the anterior chamber earlier, and to a greater degree, than within the center of the chamber. Increased signal within the posterior chamber was significantly less than in the anterior chamber, with measured increases probably attributable to volume averaging. CONCLUSIONS: These findings are consistent with the existence of an anterior diffusional pathway in the human eye. The model warrants further testing.

High-resolution MR imaging of the human eye 2005.

RATIONALE AND OBJECTIVES: We studied preparatory strategies for high-resolution human eye in vivo imaging with commercially available magnets and coils. MATERIALS AND METHODS: We imaged normal volunteers on 1.5T systems by Philips, GE, and Siemens, using commercial approximately 9 cm temporomandibular joint receive coils. Subjects fixated the nonimaged eye on a target. We compared signal (S) to tissue noise (Nt) and system noise (Ns) between images acquired with the imaged eye: 1) open, 2) held closed, 3) taped closed, and 4) taped closed with overlying water-soaked gauze. We standardized technique 4 to compare studies between manufacturers using T1-weighted parameters (repetition time/echo time/flip angle/number of signal averages = 400 ms/10-17 ms/90 degrees /4-6, in-plane resolution approximately 250 x 250 microm2; 2-3 mm slices, image time = 4.3-5.2 min). We obtained similar images of an enucleated human eye to estimate in vivo effects of microsaccades and ocular pulsations. RESULTS: Measurements of S/Nt and S/Ns gave surprising results of Nt < Ns in some instances. Ns/Nt was congruent with 1, varying approximately 20%, when the eye was taped shut and covered with water-soaked gauze. T1-weighted spin echo sequences, using technique 4, produced high-quality images with good S/Nt on all systems. Images from the three manufacturers were comparable when parameters were normalized for pulse repetition time, echo time, number of signal averages, bandwidth in Hz/pixel, and reconstruction matrix. Images of the enucleated eye produced S/Nt ratios that were comparable to in vivo images in some structures. CONCLUSIONS: Our best preparatory technique produced images with in-plane resolution of approximately 250 mum in 4-5 minutes with three commercial 1.5 T systems. The in vivo S/Nt was comparable to in vitro values in most solid tissues but decreased in most fluid compartments.

Incorporating shape prior into active contours with a sparse linear combination of training shapes: application to corpus callosum segmentation.

In this paper, a novel method of embedding shape information into level set image segmentation is proposed. Our method is based on inferring shape variations by a sparse linear combination of instances in the shape repository. Given a sufficient number of training shapes with variations, a new shape can be approximated by a linear span of training shapes associated with those variations. At each step of curve evolution the curve is moved to minimize Chan-Vese energy functional as well as toward the best approximation based on a linear combination of training samples. Although the method is general, in this paper it has been applied to the problem of segmentation of corpus callosum from 2D sagittal MR images.

Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status.

PURPOSE/OBJECTIVE(S): To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. METHODS AND MATERIALS: All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ(2), Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. RESULTS: The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016), and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. CONCLUSIONS: For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain clinically relevant.

CNS MR and CT findings associated with a clinical presentation of herpetic acute retinal necrosis and herpetic retrobulbar optic neuritis: five HIV-infected and one non-infected patients.

INTRODUCTION: This report demonstrates the spectrum of central nervous system (CNS) abnormalities observed on MR imaging and CT studies in 6 patients with clinical or pathologic diagnoses of acute retinal necrosis (ARN) and retrobulbar optic neuritis (RBON-H) resulting from Herpes Zoster Virus and Cytomegalovirus. We discuss the etiologic and pathophysiologic implications regarding these findings. METHODS: Standard MR imaging sequences of the whole brain and selected high-resolution images of the orbits and globes, from 6 patients, were reviewed by three neuroradiologists for consensus interpretation of the findings. Special sequences augmenting disease were obtained in individual cases. Axial CT images were obtained from two patients using 5mm sequential slices. RESULTS: MR imaging findings showed both T2 signal brightening and contrast enhancement in one or both optic nerves, optic tracts and lateral geniculate bodies, as well as the postsynaptic optic radiations and optic cortex. Similar findings were observed in the superior colliculus, lateral midbrain and cerebellum, with multiple potential etiologic possibilities regarding pathways of dissemination. Low T2* signal (indicating magnetic field susceptibility effects) and CT hyperdensity, consistent with prior hemorrhage, were also observed in the optic tracts, optic radiations and lateral geniculate bodies. Post-contrast enhancement was observed in the meninges and Meckle's cave in one HIV negative patient. CONCLUSION: These cases demonstrate CNS imaging findings associated with RBON that are temporally-related to ARN. They support the hypothesis that RBON can either precede or follow ARN and implicate transneuronal, transsynaptic and/or transcerebrospinal fluid viral spread by the herpetic family.

Effect of hyperbaric oxygen therapy on a murine squamous cell carcinoma model.

BACKGROUND: Hyperbaric oxygen (HBO) therapy is sometimes used to assist in wound healing after major head and neck cancer surgery. However, there is concern that HBO treatments might enhance the growth of any residual microscopic disease. This was studied in a mouse model of squamous cell carcinoma (SCC). METHODS: SCC-VII/SF tumor cells were cultured, and then injected (3 × 10(3) cells) into C3H/HeJ mice in 5 groups: subcutaneous (SQ) control (n = 13), SQ-immediate (n = 12), SQ-delayed (n = 13), tail vein control (n = 8), and tail vein immediate (n = 9). The 3 experimental groups were subjected to HBO therapy, 2.4 atm for 90 minutes, 5 days per week for 4 weeks, starting on postinjection day 3 ("immediate") or 10 ("delayed"). Tumors in the SQ mice were measured 3 times per week. Lung metastases in the tail vein mice were counted at necropsy. RESULTS: At postimplantation day 28, when the immediate group completed its HBO therapy, the tumor volume in the SQ-immediate group was 49.1% higher than the control group, and the SQ-delayed group was 105.1% higher than controls (p < .05). Two weeks later, the SQ-immediate group and SQ-delayed group tumor volumes were still significantly higher than controls, but the difference was smaller (18.4% and 43.8%, respectively; p < .05 only for the delayed group). The tail vein groups had similar numbers of lung metastases, with a mean of 8.7 metastases in the control group and 9.0 metastases in the HBO group (not significant [NS]). CONCLUSION: This study suggests that HBO therapy does accelerate the growth of microscopic foci of SCCs. This finding differs from some earlier studies and warrants further study.

Zoster paresis: asymptomatic MRI lesions far beyond the site of rash and focal weakness.

We describe a patient with zoster paresis and an MRI that revealed extensive spinal cord lesions from the upper cervical to the lower thoracic spinal cord. Importantly, the patient reported considerable spontaneous improvement in strength 2-3 weeks after zoster. This report reveals a previously undescribed remarkable preponderance of MRI lesions far beyond the site of zoster rash and focal lower motor neuron weakness.

Varicella zoster virus in the temporal artery of a patient with giant cell arteritis.

We recently detected varicella zoster virus (VZV) in the temporal arteries (TA) of 5/24 patients with clinically suspect giant cell arteritis (GCA) whose TAs were GCA-negative pathologically; in those GCA-negative, VZV+TAs, virus antigen predominated in the arterial adventitia, but without medial necrosis and multinucleated giant cells. During our continuing search for VZV antigen in GCA-negative TAs, in the TA of one subject, we found abundant VZV antigen, as well as VZV DNA, in multiple regions (skip areas) of the TA spanning 350 µm, as well as in skeletal muscle adjacent to the infected TA. Additional pathological analysis of sections adjacent to those containing viral antigen revealed inflammation involving the arterial media and abundant multinucleated giant cells characteristic of GCA. Detection of VZV in areas of the TA with pathological features of GCA warrants further correlative pathological-virological analysis of VZV in GCA.

T(1) and T(2) measurements of the fine structures of the in vivo and enucleated human eye.

PURPOSE: To measure T(1) and T(2) of the fine structures of the in vivo eye. MATERIALS AND METHODS: Involuntary saccades make it difficult to obtain artifact-free images. Using a method recently reported (Bert et al, Acad Radiol 2006;12:368-378), near artifact-free spin-echo images were obtained. Both an isolated enucleated eye and eight human subjects were studied at 1.5 T. Spin-echo variable TR/TE data was acquired for T(1)/T(2) determination. Average relaxation times were calculated two ways. First, an arithmetic average over different subjects was computed. Second, all data was normalized using the fitted amplitudes of each data set and pooled to obtain a single least squares fit. RESULTS: In vivo T(1)/T(2) (msec) are: arithmetic average T(1), T(2), normalized data T(1), T(2). Anterior chamber: 6233 +/- 979, 468 +/- 149, 5053 +/- 1052, 450 +/- 49. Ciliary body: 1916 +/- 184, 80 +/- 7, 2038 +/- 114, 76 +/- 3. Chorioretina: 1717 +/- 500, 72 +/- 25, 1511 +/- 230, 78 +/- 3. Extraocular muscle: 1581 +/- 646, 41 +/- 7, 1470 +/- 231, 41 +/- 1. Iris: 3334 +/- 989, 163 +/- 63, 3376 +/- 338, 153 +/- 10. Lens cortex: 1712 +/- 466, 93 +/- 36, 1413 +/- 177, 100 +/- 5. Lens nucleus: 1133 +/- 40, 26 +/- 3, 1138 +/- 47, 25 +/- 0.4. Optic nerve: 1906 +/- 301, 68 +/- 16, 1805 +/- 244, 71 +/- 2. Posterior chamber: 7915 +/- 4897, 241 +/- 14, 3323 +/- 2154, 251 +/- 38. Vitreous humor: 5768 +/- 1190, 756 +/- 804, 4855 +/- 1846, 390 +/- 8. CONCLUSION: In vivo T(1) and T(2) for many of the fine structures of the human eye have been measured.

Serologic responses to epitopes of the major surface glycoprotein of Pneumocystis jiroveci differ in human immunodeficiency virus-infected and uninfected persons.

The major surface glycoprotein (Msg) of Pneumocystis jiroveci (P. jiroveci) is important in the immunopathogenesis of Pneumocystis pneumonia (PcP), but is difficult to study in humans. We generated 3 overlapping recombinant Msg fragments (MsgA, MsgB and MsgC), and analyzed their reactivity with serum samples from 95 healthy blood donors and 94 human immunodeficiency virus (HIV)-infected persons. Reactivity to the Msg fragments varied with HIV infection and prior episodes of PcP but not with geographic origin. Recognition of MsgA was lower-and recognition of MsgB was significantly lower-in HIV(+) serum compared with donor serum. Serum samples from HIV-positive patients with prior PcP recognized MsgC more frequently than did serum samples from those without PcP. None of the serum samples drawn from 9 patients before they had developed PcP recognized MsgC. These data suggest that these novel recombinant proteins are useful for the analysis of antibody responses to Msg.