Catálogo de publicaciones - libros

The aim of this study was to evaluate the extent of mitochondrial injury by assessing N-Acetyl-Aspartate by MR spectroscopy in head injured patients and relating the extent of mitochondrial injury to outcome. The study population (n = 15) consisted of head injured patients (GCS < 8) in whom legal consent was obtained for MRS studies. Studies were performed on a 1.5 Tesla Vision/Siemens system. Size of Voxel equaled 8 cm with location determined from T1 images. Voxels were positioned adjacent to the lesion and in the contralateral hemisphere for focal and bilateral for diffuse. Mitochondrial impairment was considered as percent reduction in NAA/Cr ratio compared to matched controls. Mitochondrial impairment gradually increases soon after injury reaching a nadir at 10 days. Subsequently, mitochondria recover in patients with favorable outcome, but remains impaired in patients with poor outcome. The prognostic value of NAA/Cr to assist in management and also to serve as a surrogate endpoint for clinical trials appears promising.

Aneurysmal subarachnoid hemorrhage (SAH) can be complicated by reduction of regional cerebral blood flow (rCBF) from large conductance vessels leading to focal edema appearing as an area of hypoattenuation on CT. In this study we included 29 patients with SAH due to aneurysmal rupture, having 36 CT low density areas within the middle cerebral artery territory in whom a total of 56 Xenon-CT (Xe-CT) studies were performed. Collectively, we evaluated 70 hypoattenuated areas. rCBF levels were measured in two different regions of interest drawn manually on the CT scan, one in the low density area and the other in a corresponding contralateral area of normal-appearing brain tissue. In the low density area (22.6 ± 22.7 ml/100 gr/min) rCBF levels were significantly lower than in the contralateral area (32.8 ± 17.1 7 ml/100 gr/min) (p = 0.0007). In the injured areas deep ischemia (CBF < 6 ml/100 g/min) was present in only 25.7% of Xe-CT studies, suggesting that hypodense areas are not always ischemic, whereas in 43.7% of the lesions/Xe-CT studies we found hyperemic values. Patients with a better outcome had hyperemic lesions, suggesting brain tissue recovery in injured areas.

The pathogenesis and the viability of edematous tissue may be different in traumatic hematomas and traumatic contusions. We tested the hypothesis that mapping of regional Cerebral Blood Flow (rCBF) was different in these two subtypes of traumatic intraparenchymal lesions. We evaluated rCBF by means of Xenon-enhanced computerized tomography (Xe-CT) in 59 traumatic intracerebral lesions from 43 patients with severe head injury. One-hundred-nine intracerebral lesions/Xe-CT CBF measurements were obtained. The rCBF was measured in the hemorrhagic core, in the intralesional oedematous low density area and in a 1 cm rim of apparently normal perilesional parenchyma of both lesion subtypes. Not statistically significant lower rCBF levels were found in the edematous area of traumatic contusions. In traumatic hematomas rCBF levels were lower in the core than in the low density area, suggesting that rCBF in edematous area is marginally involved in the initial traumatic injury and that edema is probably influenced by the persistence of the hemorrhagic core. Conversely, in the traumatic contusions a difference in rCBF values was found between core, low density area and perilesional area, indicating that rCBF of the low density area is related to a concentrical distribution of the initial injury.

Following traumatic brain injury, as a consequence of ionic disturbances and neurochemical cascades, glucose metabolism is affected. [F]-2-Fluoro-2-deoxy-D-glucose (FDG) — Positron Emission Tomography (FDG-PET) provides a measure of global and regional cerebral metabolic rate of glucose (rCMRglc), but only during the time of the scan. Microdialysis monitors energy metabolites over extended time periods, but only in a small focal volume of the brain.

Our objective in this study is to assess the association of parameters derived from these techniques when applied to patients with traumatic brain injury. Eleven sedated, ventilated patients receiving intracranial pressure monitoring and managed using Addenbrooke’s Neurosciences Critical Care Unit protocols were monitored. Dialysate values for glucose, lactate, pyruvate, and glutamate, and the lactate to glucose (L/G), lactate to pyruvate (L/P) and pyruvate to glucose (P/G) ratios were determined and correlated with rCMRglc.

FDG-PET scans were performed within 24 hours (five patients), or between 1 and 4 days (two patients) or after 4 days (six patients). Two patients were rescanned 4 and 7 days after their initial scan. A 20 mm region of interest (ROI) was defined on co-registered CT scan on two contiguous slices around the microdialysis catheter. Mean (±sd) for rCMRglc was 19.1 ± 5.5 µmol/100 g/min, and the corresponding microdialysis values were: glucose 1.4 ± 1.4 mmol/L; lactate 5.3 ± 3.6 mmol/L; pyruvate 164.1 ± 142.3 µmol/L; glutamate 15.0 ± 14.7 µmol/L; L/G 11.0 ± 16.0; L/P 27.3 ± 7.9 and P/G 381 ± 660. There were significant relations between rCMRglc and dialysate lactate (r = 0.58, P = 0.04); pyruvate (r = 0.57, P = 0.04), L/G (r = 0.55, P = 0.05), and the P/G (r = 0.56, P = 0.05) but not between rCMRglc and dialysate glucose, L/P or glutamate in this data set.

The results suggest that increases in glucose utilization as assessed by FDG-PET in these patients albeit in mainly healthy tissue are associated with increases in dialysate lactate, pyruvate, L/G and the P/G ratio perhaps indicating a general rise in metabolism rather than a shift towards non-oxidative metabolism. Further observations are required with regions of interest (microdialysis catheters positioned) adjacent to mass lesions notably contusions.

The objective of the study was to evaluate radiation-induced cerebral injury on dynamic susceptibility contrast-enhanced (DSCE) perfusion MR imaging and study its relationship with morphological severity and disease progression.

Thirty-one patients with known radiation injury to the temporal lobes where studied. Gradient and spin-echo T2-weighted, gadolinium-enhanced T1-weighted and DSCE perfusion MR imaging were obtained in the coronal plane through the anterior temporal lobe. Regions of interest where selected in the anterior temporal lobes and the superior frontal lobe as control for analysis of perfusion parameters.

The mean transit time (MTT) was prolonged in both the High Dose Zone (HDZ) receiving from two-thirds to the total dose of 66–71. 2 Gy, and the Intermediary Dose Zone (IDZ) receiving up to 87% of the total dose. The HDZ but not the IDZ showed a low relative cerebral blood volume (rCBV) and relative cerebral blood flow index (rCBFi). The rCBV and rCBFi were significantly lower in both HDZ and LBZ in temporal lobes with severe lesions compared to the temporal lobes with mild lesions but there was no significant difference in bolus transit parameters. The rCBV and rCBFi were significantly lower in both HDZ and IDZ of the swollen temporal lobes compared to those without swelling.

It was concluded that DSCE perfusion MR imaging demonstrated a derangement in perfusion in radiation-induced cerebral injury in rCBV, rCBFi and MTT, which were related to the severity of the radiation-induced injury and the dose of irradiation delivered.

Postural related changes in cerebral hemodynamics and hydrodynamics were studied using Magnetic Resonance Imaging (MRI) measurements of cerebral blood flow and cerebrospinal fluid (CSF) flow dynamics. Ten healthy volunteers (mean age 29 ± 7) were studied in supine and upright (sitting) postures. A Cine phase-contrast MRI technique was used to image the pulsatile blood flow to the brain, the venous outflow through the internal jugular, epidural, and vertebral veins, and the bi-directional CSF flow between the cranium and the spinal canal. Previously published analyses were applied to calculate and compare total cerebral blood flow (TCBF), intracranial compliance and pressure in both postures. A lower (12%) mean TCBF was measured in the upright position compared to supine position. A considerable smaller amount of CSF flow between the cranium and the spinal canal (58%), a much larger intracranial compliance (a 2.8-fold increase), and a corresponding decrease in the MRI-derived ICP were also measured in the sitting position. These changes suggest that the increased cerebrovascular and intracranial compliances in the upright posture are primarily due to reduced amounts of blood and CSF residing in their respective intracranial compartments in the upright position. This work demonstrates the ability to quantify neurophysiologic parameters associated with regulation of cerebral hemodynamics and hydrodynamics from dynamic MR imaging of blood and CSF flows.

To confirm the reliability of a refill kinetic method of ultrasonic harmonic perfusion imaging (HPI) capable of quantifying separate parameters of microvascular blood flow velocity and volume in brain tissue, we evaluated acetazolamide (ACZ) cerebrovascular reactivity by transcranial HPI in comparison with Doppler sonography (TCD).

. HPI during continuous Levovist™ infusion with changing pulsing intervals (t) and TCD time-averaged maximum velocity (TAMX) in the middle and posterior cerebral arteries were evaluated before and after ACZ administration in 12 patients, 8 without and 4 with a temporal skull defect. Plateau value (A) and rise rate (β) of intensity (I) represented by HPI time-intensity curves of I(t) = A(1 − e) were analyzed on the axial diencephalic plane.

. 1) A significantly decreased in proportion to the region of interest location depth only in the intact skull cases. 2) Despite interand intra-individual data scattering, in correspondence with TAMX increases after ACZ, significant β increases were more frequently identified than increases of A.

. Cerebral vasoreactivity analysis utilizing refill kinetics of transcranial HPI can potentially provide separate quantification based on microvascular blood velocity and volume (capillary patency) with consideration of depth-dependant ultrasound attenuation. This should be suitable for bedside evaluation of neurointensive care patients.

Cerebral blood flow and ICP are important neurophysiologic parameters known to be affected by pathology and by trauma. Limited data on the relationship between these parameters following head trauma is inconsistent with regard to whether these parameters are correlated. Data on the relationship between these parameters in the healthy state is not readily available due to a lack of noninvasive means to measure these important parameters. A recently developed noninvasive MRI-based method for simultaneous measurement of total cerebral blood flow and intracranial pressure was applied to establish the relationship between ICP and TCBF values in healthy subjects. Seventy-one simultaneous measurements of CBF and ICP were obtained from 23 healthy young adults. These results demonstrated that CBF values span over a much narrower range compared with ICP. The relationship between the inter-individual CBF and ICP measurements suggest that in the healthy state and in rest these parameters are not correlated.