Guadalupe Soria

Acute damage to the posterior limb of the internal capsule on diffusion tensor tractography as an early imaging predictor of motor outcome after stroke.

Practical applications of diffusion tensor imaging are few, but this seems to be an interesting and a potentially important one: can it be used to predict motor outcome after stroke? Sixty patients within 12 hours of stroke were assessed with tractography at 5 different locations in the corticospinal tracts at admission, and at days 3 and 30. Patients with acute damage to the posterior limb of the internal capsule had the worst outcome and clinical severity at presentation. Conclusions: In the acute setting, tractography is promising for stroke mapping to predict motor outcome. Acute corticospinal tract damage at the level of the posterior limb of the internal capsule is a significant predictor of unfavorable motor outcome. BACKGROUND AND PURPOSE: Early prediction of motor outcome is of interest in stroke management. We aimed to determine whether lesion location at DTT is predictive of motor outcome after acute stroke and whether this information improves the predictive accuracy of the clinical scores. MATERIALS AND METHODS: We evaluated 60 consecutive patients within 12 hours of middle cerebral artery stroke onset. We used DTT to evaluate CST involvement in the motor cortex and premotor cortex, centrum semiovale, corona radiata, and PLIC and in combinations of these regions at admission, at day 3, and at day 30. Severity of limb weakness was assessed by using the motor subindex scores of the National Institutes of Health Stroke Scale (5a, 5b, 6a, 6b). We calculated volumes of infarct and fractional anisotropy values in the CST of the pons. RESULTS: Acute damage to the PLIC was the best predictor associated with poor motor outcome, axonal damage, and clinical severity at admission (P < .001). There was no significant correlation between acute infarct volume and motor outcome at day 90 (P = .176, r = 0.485). The sensitivity, specificity, and positive and negative predictive values of acute CST involvement at the level of the PLIC for motor outcome at day 90 were 73.7%, 100%, 100%, and 89.1%, respectively. In the acute stage, DTT predicted motor outcome at day 90 better than the clinical scores (R2 = 75.50, F = 80.09, P < .001). CONCLUSIONS: In the acute setting, DTT is promising for stroke mapping to predict motor outcome. Acute CST damage at the level of the PLIC is a significant predictor of unfavorable motor outcome.

Quantification of thrombus Hounsfield units on noncontrast CT predicts stroke subtype and early recanalization after intravenous recombinant tissue plasminogen activator

Anecdotally we know that high-density clots are probably more organized and difficult to lyse. These investigators calculated HU values for MCA thrombi on noncontrast CT within 4.5 hours of symptom onset and correlated it with successful recanalization after intravenous tPA treatment given 169 +/− 102 minutes thereafter. Best outcomes were achieved for M1, low-density, and thrombi not originating from the heart. Worse outcomes were related to high-density thrombi and those originating from the heart. BACKGROUND AND PURPOSE: Little is known about the factors that determine recanalization after intravenous thrombolysis. We assessed the value of thrombus Hounsfield unit quantification as a predictive marker of stroke subtype and MCA recanalization after intravenous rtPA treatment. MATERIALS AND METHODS: NCCT scans and CTA were performed on patients with MCA acute stroke within 4.5 hours of symptom onset. Demographics, stroke severity, vessel hyperattenuation, occlusion site, thrombus length, and time to thrombolysis were recorded. Stroke origin was categorized as LAA, cardioembolic, or indeterminate according to TOAST criteria. Two blinded neuroradiologists calculated the Hounsfield unit values for the thrombus and contralateral MCA segment. We used ROC curves to determine the rHU cutoff point to discriminate patients with successful recanalization from those without. We assessed the accuracy (sensitivity, specificity, and positive and negative predictive values) of rHU in the prediction of recanalization. RESULTS: Of 87 consecutive patients, 45 received intravenous rtPA and only 15 (33.3%) patients had acute recanalization. rHU values and stroke mechanism were the highest predictive factors of recanalization. The Matthews correlation coefficient was highest for rHU (0.901). The sensitivity, specificity, and positive and negative predictive values for lack of recanalization after intravenous rtPA for rHU ≤ 1.382 were 100%, 86.67%, 93.75%, and 100%, respectively. LAA thrombi had lower rHU than cardioembolic and indeterminate stroke thrombi (P = .004). CONCLUSIONS: The Hounsfield unit thrombus measurement ratio can predict recanalization with intravenous rtPA and may have clinical utility for endovascular treatment decision making.

Quantitative discrimination between endogenous SHG sources in mammalian tissue, based on their polarization response

In this study, the second harmonic generation (SHG) response to polarization and subsequent data analysis is used to discriminate, in the same image, different SHG source architectures with pixel resolution. This is demonstrated in a mammalian tissue containing both skeletal muscle and fibrilar collagen. The SHG intensity variation with the input polarization (PSHG) is fitted pixel by pixel in the image using an algorithm based on a generalized biophysical model. The analysis provides the effective orientation, theta(e), of the different SHG active structures (harmonophores) at every pixel. This results in a new image in which collagen and muscle are clearly differentiated. In order to quantify the SHG response, the distribution of theta(e) for every harmonophore is obtained. We found that for collagen, the distribution was centered at theta(e) = 42.7 degrees with a full width at half maximum of theta = 5.9 degrees while for muscle theta(e) = 65.3 degrees , with theta = 7.7 degrees . By comparing these distributions, a quantitative measurement of the discrimination procedure is provided.

In vivo magnetic resonance imaging characterization of bilateral structural changes in experimental Parkinson's disease: a T2 relaxometry study combined with longitudinal diffusion tensor imaging and manganese-enhanced magnetic resonance imaging in the 6-hydroxydopamine rat model

The neuropathological hallmark of Parkinson’s disease is the loss of dopaminergic neurons in the pars compacta of the substantia nigra (SNc). The degenerative process starts unilaterally and spreads to the dopaminergic system of both hemispheres. However, the complete characterization of the nigra lesion and the subsequent changes in basal ganglia nuclei activity has not yet been achieved in vivo. The aim of this study was to characterize the time course of the nigral lesion in vivo, using longitudinal T2 relaxometry and diffusion tensor imaging, and the changes in basal ganglia nuclei activity, using manganese‐enhanced magnetic resonance imaging, in 6‐hydroxydopamine (6‐OHDA)‐lesioned rats. Our results showed that a unilateral SNc lesion induces bilateral alterations, as indicated by the enhancement of magnetic resonance imaging T2 relaxation times in both the ipsilateral and contralateral SNc. Moreover, axial and radial diffusivities demonstrated bilateral changes at 3 and 14 days after 6‐OHDA injection in the pars reticulata of the substantia nigra and cortex, respectively, in comparison to the sham group, suggesting bilateral microstructural alterations in these regions. Unexpectedly, manganese‐enhanced magnetic resonance imaging showed decreased axonal transport from the ipsilateral subthalamic nucleus to the ventral pallidum in 6‐OHDA‐lesioned animals compared with the sham group. These findings demonstrate, for the first time in vivo, the temporal pattern of bilateral alteration induced by the 6‐OHDA model of Parkinson’s disease, and indicate decreased axonal transport in the ipsilateral hemisphere.

Estimation of the effective orientation of the SHG source in primary cortical neurons

In this paper we provide, for the first time to our knowledge, the effective orientation of the SHG source in cultured cortical neuronal processes in vitro. This is done by the use of the polarization sensitive second harmonic generation (PSHG) imaging microscopy technique. By performing a pixel-level resolution analysis we found that the SHG dipole source has a distribution of angles centered at thetae =33.96 degrees , with a bandwidth of Deltathetae = 12.85 degrees . This orientation can be related with the molecular geometry of the tubulin heterodimmer contained in microtubules.

The Ins and Outs of the BCCAo Model for Chronic Hypoperfusion: A Multimodal and Longitudinal MRI Approach

Cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAo) in rodents has been proposed as an experimental model of white matter damage and vascular dementia. However, the histopathological and behavioral alterations reported in this model are variable and a full characterization of the dynamic alterations is not available. Here we implemented a longitudinal multimodal magnetic resonance imaging (MRI) design, including time-of-flight angiography, high resolution T1-weighted images, T2 relaxometry mapping, diffusion tensor imaging, and cerebral blood flow measurements up to 12 weeks after BCCAo or sham-operation in Wistar rats. Changes in MRI were related to behavioral performance in executive function tasks and histopathological alterations in the same animals. MRI frequently (70%) showed various degrees of acute ischemic lesions, ranging from very small to large subcortical infarctions. Independently, delayed MRI changes were also apparent. The patterns of MRI alterations were related to either ischemic necrosis or gliosis. Progressive microstructural changes revealed by diffusion tensor imaging in white matter were confirmed by observation of myelinated fiber degeneration, including severe optic tract degeneration. The latter interfered with the visually cued learning paradigms used to test executive functions. Independently of brain damage, BCCAo induced progressive arteriogenesis in the vertebrobasilar tree, a process that was associated with blood flow recovery after 12 weeks. The structural alterations found in the basilar artery were compatible with compensatory adaptive changes driven by shear stress. In summary, BCCAo in rats induces specific signatures in multimodal MRI that are compatible with various types of histological lesion and with marked adaptive arteriogenesis.

Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats

Background and aim The lymphatic network plays a major role in maintaining tissue fluid homoeostasis. Therefore several pathological conditions associated with oedema formation result in deficient lymphatic function. However, the role of the lymphatic system in the pathogenesis of ascites and oedema formation in cirrhosis has not been fully clarified. The aim of this study was to investigate whether the inability of the lymphatic system to drain tissue exudate contributes to the oedema observed in cirrhosis. Methods Cirrhosis was induced in rats by CCl4 inhalation. Lymphatic drainage was evaluated using fluorescent lymphangiography. Expression of endothelial nitric oxide synthase (eNOS) was measured in primary lymphatic endothelial cells (LyECs). Inhibition of eNOS activity in cirrhotic rats with ascites (CH) was carried out by L-NG-methyl-L-arginine (L-NMMA) treatment (0.5 mg/kg/day). Results The (CH) rats had impaired lymphatic drainage in the splanchnic and peripheral regions compared with the control (CT) rats. LyECs isolated from the CH rats showed a significant increase in eNOS and nitric oxide (NO) production. In addition, the lymphatic vessels of the CH rats showed a significant reduction in smooth muscle cell (SMC) coverage compared with the CT rats. CH rats treated with L-NMMA for 7 days showed a significant improvement in lymphatic drainage and a significant reduction in ascites volume, which were associated with increased plasma volume. This beneficial effect of L-NMMA inhibition was also associated with a significant increase in lymphatic SMC coverage. Conclusions The upregulation of eNOS in the LyECs of CH rats causes long-term lymphatic remodelling, which is characterised by a loss of SMC lymphatic coverage. The amelioration of this lymphatic abnormality by chronic eNOS inhibition results in improved lymphatic drainage and reduced ascites.

The use of a three-dimensional novel computer-based model for analysis of the endonasal endoscopic approach to the midline skull base.

OBJECTIVES To apply a three-dimensional geometric model to various endoscopic endonasal approaches to analyze the bony anatomy of this area, quantify preoperatively bone removal, and optimize surgical planning. METHODS Investigators dissected 18 human cadaveric heads at the Laboratory of Surgical NeuroAnatomy (LSNA) of the University of Barcelona (Spain). Before and after each dissection, a computed tomography (CT) scan was performed to create a three-dimensional geometric model of the approach performed in the dissection room. The model protocol was designed as follows: (i) a preliminary exploration of each specimen using the preoperative CT scan, (ii) creation of a computer-generated three-dimensional virtual model of the approach, (iii) cadaveric anatomic dissection, and (iv) development of a CT-based model of the approach as a result of the superimposition of predissection and postdissection digital imaging and communications in medicine (DICOM) images of specimens. RESULTS This method employing preliminary virtual exploration of each specimen, the creation of a three-dimensional virtual model of the approach, and the overlapping of the predissection and postdissection three-dimensional models was useful to define the exact boundaries of the endoscopic endonasal craniectomy. CONCLUSIONS Aside from laboratory anatomic dissection itself, this model is very effective in providing a depiction of bony landmarks and visual feedback of the amount of bone removed, improving the design of the craniectomy in the endoscopic endonasal midline skull base approach.

Bicosomes: Bicelles in dilute systems

Bicelles are discoidal phospholipid nanostructures at high lipid concentrations. Under dilute conditions, bicelles become larger and adopt a variety of morphologies. This work proposes a strategy to preserve the discoidal morphology of bicelles in environments with high water content. Bicelles were formed in concentrated conditions and subsequently encapsulated in liposomes. Later dilution of these new structures, called bicosomes, demonstrated that lipid vesicles were able to isolate and protect bicelles entrapped inside them from the medium. Characterization of systems before and after dilution by dynamic light-scattering spectroscopy and cryo-transmission electron microscopy showed that free bicelles changed in size and morphology, whereas encapsulated bicelles remained unaltered by the effect of dilution. Free and entrapped bicelles (containing the paramagnetic contrast agent gadodiamide) were injected into rat brain lateral ventricles. Coronal and sagittal visualization was performed by magnetic resonance imaging. Whereas rats injected with free bicelles did not survive the surgery, those injected with bicosomes did, and a hyperintensity effect due to gadodiamide was observed in the cerebrospinal fluid. These results indicate that bicosomes are a good means of preserving the morphology of bicelles under dilution conditions.

A complementary diffusion tensor imaging (DTI)-histological study in a model of Huntington's disease

In vivo diffusion tensor imaging (DTI) was performed on the quinolinic acid (QUIN) rat model of Huntingtons disease, together with behavioral assessment of motor deficits and histopathological characterization. DTI and histology revealed the presence of a cortical lesion in 53% of the QUIN animals (QUIN(+ctx)). Histologically, QUIN(+ctx) were distinguished from QUIN(-ctx) animals by increased astroglial reaction within a subregion of the caudate putamen and loss of white matter in the external capsula. Although both techniques are complementary, the quantitative character of DTI makes it possible to pick up subtle differences in tissue microstructure that are not identified with histology. DTI demonstrated differential changes of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in the internal and external capsula, and within a subregion of the caudate putamen. It was suggested that FA increased due to a selective loss of the subcortical connections targeted by degenerative processes at the early stage of the disease, which might turn the striatum into a seemingly more organized structure. When tissue degeneration becomes more severe, FA decreased while AD, RD and MD increased.