A Peña

University of Cambridge, Cambridge, England, United Kingdom

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Publications (29)89.81 Total impact

  • Journal of Critical Care 06/2012; 27(3):e9–e10. DOI:10.1016/j.jcrc.2012.01.029 · 2.00 Impact Factor
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    ABSTRACT: Higher biologic systems operate far from equilibrium resulting in order, complexity, fluctuation of inherent parameters, and dissipation of energy. According to the decomplexification theory, disease is characterized by a loss of system complexity. We analyzed such complexity in patients after subarachnoid hemorrhage (SAH), by applying the standard technique of variability analysis and the novel method of fractal analysis to middle cerebral artery blood flow velocity (FV) and arterial blood pressure (ABP). In 31 SAH -patients, FV (using transcranial Doppler sonography) and direct ABP were measured. The standard deviations (s.d.) and coefficients of variation (CV=relative s.d.) for FV and ABP time series of length 2(10) secs were calculated as measures of variability. The spectral index beta(low) and the Hurst coefficient H(bdSWV) were analyzed as fractal measures. Outcome was assessed 1 year after SAH according to the Glasgow Outcome Scale (GOS). Both FV (beta(low)=2.2+/-0.4, mean+/-s.d.) and ABP (beta(low)=2.3+/-0.4) were classified as nonstationary (fractal Brownian motion) signals. FV showed significantly (P<0.05) higher variability (CV=7.2+/-2.5%) and Hurst coefficient (H(bdSWV)=0.26+/-0.13) as compared with ABP (CV=5.5+/-2.7%, H(bdSWV)=0.19+/-0.11). Better outcome (GOS) correlated significantly (P<0.05) with higher s.d. of FV (Spearman's r(s)=0.51, r(s)(2)=0.26) and ABP (r(s)=0.57, r(s)(2)=0.32), as well as with a higher Hurst coefficient of ABP (r(s)=0.46, r(s)(2)=0.21). Cerebral vasospasm reduced CV of FV, but left H(bdSWV) unchanged. FV and ABP fluctuated markedly despite homeostatic control. A reduced variability of FV and ABP might indicate a loss of complexity and was associated with a less favorable outcome. Therefore, the decomplexification theory of illness may apply to SAH.
    Journal of Cerebral Blood Flow & Metabolism 02/2008; 28(1):64-73. DOI:10.1038/sj.jcbfm.9600506 · 5.41 Impact Factor
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    ABSTRACT: The efficacy of radiation therapy, the mainstay of treatment for malignant gliomas, is limited by our inability to accurately determine tumor margins. As a result, despite recent advances, the prognosis remains appalling. Because gliomas preferentially infiltrate along white matter tracks, methods that show white matter disruption should improve this delineation. In this study, results of histologic examination from samples obtained from image-guided brain biopsies were correlated with diffusion tensor images. Twenty patients requiring image-guided biopsies for presumed gliomas were imaged preoperatively. Patients underwent image-guided biopsies with multiple biopsies taken along a single track that went into normal-appearing brain. Regions of interest were determined from the sites of the biopsies, and diffusion tensor imaging findings were compared with glioma histology. Using diffusion tissue signatures, it was possible to differentiate gross tumor (reduction of the anisotropic component, q > 12% from contralateral region), from tumor infiltration (increase in the isotropic component, p > 10% from contralateral region). This technique has a sensitivity of 98% and specificity of 81%. T2-weighted abnormalities failed to identify the margin in half of all specimens. Diffusion tensor imaging can better delineate the tumor margin in gliomas. Such techniques can improve the delineation of the radiation therapy target volume for gliomas and potentially can direct local therapies for tumor infiltration.
    American Journal of Neuroradiology 11/2006; 27(9):1969-74. · 3.59 Impact Factor
  • M. Soehle · D. A. Chatfield · M. Czosnyka · A. Pena ·

    European Journal of Anaesthesiology 06/2006; 23(Supplement 37). DOI:10.1097/00003643-200606001-00341 · 2.94 Impact Factor
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    ABSTRACT: Cerebral oedema, it has been suggested, may have a role in the pathophysiology of benign intracranial hypertension (BIH). We applied diffusion tensor MR imaging (DTI), a technique able to detect cerebral oedema, to the study of patients with BIH. A quantitative regional analysis of diffusion parameters (trace and relative anisotropy) was conducted by comparing five BIH patients and six healthy controls. A small but significant increase in anisotropy accompanied by a small but significant decrease in trace was found in the putamen and head of the caudate nucleus. No significant changes were demonstrated in the thalamus, cerebral white matter or cortical regions. Our findings support other recent work that suggests cerebral oedema is not a factor in the pathogenesis of BIH.
    British Journal of Neurosurgery 05/2006; 20(2):79-81. DOI:10.1080/02688690600682317 · 0.96 Impact Factor
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    ABSTRACT: Background. The authors present a patient who developed transient hemispatial neglect following surgical drainage of a large right frontotemporal arachnoid cyst. As symptoms evolved in parallel with brain shift over the subsequent months, the authors hypothesized that the disorder was associated with the appearance of mechanical stresses in the cerebral mantle. Methods. To map tissue stress at the various stages of deformation, a finite element computer simulation was conducted on the basis of computed tomography scans of the patient. Results. The authors' results demonstrate substantial shear and compressive stress concentrations in the parietal lobe, a region commonly associated with neglect, and where positron emission tomography confirmed hypoperfusion in this patient. Treatment with combined ventricular-peritoneal and cystoperitoneal shunts was accompanied by clinical recovery and improvement of right parietal lobe cerebral blood flow. Conclusions. The authors conclude that brain deformation was a contributing factor in the reversible neglect syndrome by compromising the normal flow of blood and/or the deactivation of subcortical circuits of the parietal lobe.
    Journal of neuroimaging: official journal of the American Society of Neuroimaging 02/2006; 12(4):360 - 367. DOI:10.1111/j.1552-6569.2002.tb00145.x · 1.73 Impact Factor
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    ABSTRACT: Many scalar measures have been proposed to quantify magnetic resonance diffusion tensor imaging (MR DTI) data in the brain. However, only two parameters are commonly used in the literature: mean diffusion (D) and fractional anisotropy (FA). We introduce a visualization technique which permits the simultaneous analysis of an additional five scalar measures. This enhanced diversity is important, as it is not known a priori which of these measures best describes pathological changes for brain tissue. The proposed technique is based on a tensor transformation, which decomposes the diffusion tensor into its isotropic (p) and anisotropic (q) components. To illustrate the use of this technique, diffusion tensor imaging was performed on a healthy volunteer, a sequential study in a patient with recent stroke, a patient with hydrocephalus and a patient with an intracranial tumour. Our results demonstrate a clear distinction between different anatomical regions in the normal volunteer and the evolution of the pathology in the patients. In the normal volunteer, the brain parenchyma values for p and q fell into a narrow band with 0.976<p<1.063 x 10(-3) mm2 s(-1) and 0.15<q<1.08 x 10(-3) mm2 s(-1). The noise appeared as a compact cluster with (p,q) components (0.011, 0.141) x 10(-3) mm2 s(-1), while the cerebrospinal fluid was (3.320, 0.330) x 10(-3) mm2 s(-1). In the stroke patient, the ischaemic area demonstrated a trajectory composed of acute, sub-acute and chronic phases. The components of the lesion were (0.824, 0.420), (0.884, 0.254), (2.624, 0.325) at 37 h, 1 week and 1 month, respectively. The internal capsule of the hydrocephalus patient demonstrated a larger dispersion in the p:q plane suggesting disruption. Finally, there was clear white matter tissue destruction in the tumour patient. In summary, the p:q decomposition enhances the visualization and quantification of MR DTI data in both normal and pathological conditions.
    British Journal of Radiology 02/2006; 79(938):101-9. DOI:10.1259/bjr/24908512 · 2.03 Impact Factor
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    ABSTRACT: Diffusion tensor imaging (DTI) provides a unique insight into the cellular integrity of the brain. While conventional magnetic resonance imaging underestimates the extent of pathology following closed head injury, diffusion-weighted imaging has been shown to more accurately delineate the extent of cerebral damage. There have only been a few case studies of DTI in chronic head injury survivors. This study used DTI to investigate changes in anisotropy and diffusivity in survivors of head injury at least 6 months after their injury. The relationship between cognition and diffusion abnormality was also investigated. The voxel-based analysis revealed significant bilateral decreases in anisotropy, in major white matter tracts and association fibers in the temporal, frontal, parietal and occipital lobes. Statistically significant increases in diffusivity were also found in widespread areas of the cortex. A significant positive correlation was found between diffusivity and impairment of learning and memory in the left posterior cingulate, left hippocampal formation and left temporal, frontal and occipital cortex. The common pattern of abnormality despite heterogeneous injury mechanism and lesion location in the group suggests that these cellular changes reflect secondary insults. The importance of diffusion abnormalities in head injury outcome is emphasized by the significant correlation between a learning and memory index and diffusivity in areas known to subserve this cognitive function.
    NeuroImage 02/2006; 29(1):117-24. DOI:10.1016/j.neuroimage.2005.07.012 · 6.36 Impact Factor
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    ABSTRACT: Vulnerability of the hippocampus to traumatic brain injury (TBI) in adults is related to severity of injury and white matter atrophy. The objectives of this study were to determine features of anthropometry and cerebral morphometry late after TBI in childhood and to assess whether hippocampal volume is related to severity of initial ictus and changes in white matter at follow-up. Thirty-three patients underwent magnetic resonance imaging 4.9 y after severe TBI that necessitated intensive care; 23 had mechanical ventilation and intracranial pressure monitoring longer than 3 d. Magnetic resonance imaging analyses included volume of brain, hemisphere, ventricles, and hippocampal and perihippocampal regions; spatial distribution of voxel-based morphometry differences in white matter; and eigenvalues of diffusion tensor imaging diffusivity. Patients with longer intensive care ictus had smaller-than-expected occipitofrontal head circumference. Eight of these, identified by voxel-based morphometry, had periventricular white matter loss and smaller-than-expected brain volume for OFC, suggesting "atrophy"; the remainder had expected volume for a smaller OFC, suggesting "growth disturbance." Ninety-three percent of the variation in right hippocampal volume was accounted for by factors related to severity of injury and white matter atrophy. It is concluded that anthropometry and cerebral morphometric measurements late after severe TBI in childhood provides useful outcome data and indicate that, despite adequate growth in stature, effects of TBI on brain growth and hippocampal volume may extend into adulthood.
    Pediatric Research 09/2005; 58(2):302-8. DOI:10.1203/01.PDR.0000169965.08854.25 · 2.31 Impact Factor
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    ABSTRACT: The heterogeneity of the initial insult and subsequent pathophysiology has made both the study of human head injury and design of randomised controlled trials exceptionally difficult. The combination of multimodality bedside monitoring and functional brain imaging positron emission tomography (PET) and magnetic resonance (MR), incorporated within a Neurosciences Critical Care Unit, provides the resource required to study critically ill patients after brain injury from initial ictus through recovery from coma and rehabilitation to final outcome. Methods to define cerebral ischemia in the context of altered cerebral oxidative metabolism have been developed, traditional therapies for intracranial hypertension re-evaluated and bedside monitors cross-validated. New modelling and analytical approaches have been developed.
    Acta neurochirurgica. Supplement 02/2005; 95:459-64. DOI:10.1007/3-211-32318-X_94
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    ABSTRACT: We analyzed the properties of the logarithm of the Rician distribution leading to a full characterization of the probability law of the errors in the linearized diffusion tensor model. An almost complete lack of bias, a simple relation between the variance and the signal-to-noise ratio in the original complex data, and a close approximation to normality facilitated estimation of the tensor components by an iterative weighted least squares algorithm. The theory of the linear model has also been used to derive the distribution of mean diffusivity, to develop an informative statistical test for relative lack of fit of the ellipsoidal (or spherical) model compared to an unrestricted linear model in which no specific shape is assumed for the diffusion process, and to estimate the signal-to-noise ratios in the original data. The false discovery rate (FDR) has been used to control thresholds for statistical significance in the context of multiple comparisons at voxel level. The methods are illustrated by application to three diffusion tensor imaging (DTI) datasets of clinical interest: a healthy volunteer, a patient with acute brain injury, and a patient with hydrocephalus. Interestingly, some salient features, such as a region normally comprising the basal ganglia and internal capsule, and areas of edema in patients with brain injury and hydrocephalus, had patterns of error largely independent from their mean diffusivities. These observations were made in brain regions with sufficiently large signal-to-noise ratios (>2) to justify the assumptions of the log Rician probability model. The combination of diffusivity and its error may provide added value in diagnostic DTI of acute pathologic expansion of the extracellular fluid compartment in brain parenchymal tissue.
    Human Brain Mapping 02/2005; 24(2):144-55. DOI:10.1002/hbm.20076 · 5.97 Impact Factor
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    ABSTRACT: The controlled cortical impact model has been used extensively to study focal traumatic brain injury. Although the impact variables can be well defined, little is known about the biomechanical trauma as delivered to different brain regions. This knowledge however could be valuable for interpretation of experiment (immunohistochemistry etc.), especially regarding the comparison of the regional biomechanical severity level to the regional magnitude of the trauma sequel under investigation. We used finite element (FE) analysis, based on high resolution T2-weighted MRI images of rat brain, to simulate displacement, mean stress, and shear stress of brain during impact. Young's Modulus E, to describe tissue elasticity, was assigned to each FE in three scenarios: in a constant fashion (E = 50 kPa), or according to the MRI intensity in a linear (E = [10, 100] kPa) and inverse-linear fashion (E = [100, 10] kPa). Simulated tissue displacement did not vary between the 3 scenarios, however mean stress and shear stress were largely different. The linear scenario showed the most likely distribution of stresses. In summary, FE analysis seems to be a suitable tool for biomechanical simulation, however, to be closest to reality tissue elasticity needs to be determined with a more specific approach, e.g. by means of MRI elastography.
    Acta neurochirurgica. Supplement 02/2005; 95:333-6. DOI:10.1007/3-211-32318-X_68
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    Cerebrospinal Fluid Research 12/2004; 1(Suppl 1). DOI:10.1186/1743-8454-1-S1-S14 · 1.81 Impact Factor
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    ABSTRACT: The inherent invasiveness of malignant cells is a major determinant of the poor prognosis of cerebral gliomas. Diffusion tensor MRI (DTI) can identify white matter abnormalities in gliomas that are not seen on conventional imaging. By breaking down DTI into its isotropic (p) and anisotropic (q) components, we can determine tissue diffusion "signatures". In this study we have characterised these abnormalities in peritumoural white matter tracts. Thirty-five patients with cerebral gliomas and seven normal volunteers were imaged with DTI and T2-weighted sequences at 3 T. Displaced, infiltrated and disrupted white matter tracts were identified using fractional anisotropy (FA) maps and directionally encoded colour maps and characterised using tissue signatures. The diffusion tissue signatures were normal in ROIs where the white matter was displaced. Infiltrated white matter was characterised by an increase in the isotropic component of the tensor (p) and a less marked reduction of the anisotropic component (q). In disrupted white matter tracts, there was a marked reduction in q and increase in p. The direction of water diffusion was grossly abnormal in these cases. Diffusion tissue signatures may be a useful method of assessing occult white matter infiltration.
    European Radiology 11/2004; 14(10):1909-17. DOI:10.1007/s00330-004-2381-6 · 4.01 Impact Factor
  • S J Price · A Peña · N G Burnet · J D Pickard · J H Gillard ·
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    ABSTRACT: We present a patient with a recurrent glioblastoma and abnormalities of the corpus callosum seen on diffusion tensor MRI that were not seen on conventional imaging. These abnormalities preceded the development of the tumour. We describe the technique of diffusion tissue signatures to assess tissue infiltration by tumours compared with values from normal volunteers.
    British Journal of Neurosurgery 09/2004; 18(4):391-5. DOI:10.1080/02688690400005255 · 0.96 Impact Factor
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    ABSTRACT: The combination of cerebral blood flow measurement using (15)O-water positron emission tomography with magnetic resonance coregistration and CSF infusion studies was used to study the global and regional changes in CBF with changes in CSF pressure in 15 patients with normal pressure hydrocephalus. With increases in CSF pressure, there was a variable increase in arterial blood pressure between individuals and global CBF was reduced, including in the cerebellum. Regionally, mean CBF decreased in the thalamus and basal ganglia, as well as in white matter regions. These reductions in CBF were significantly correlated with changes in the CSF pressure and with proximity to the ventricles. A three-dimensional finite-element analysis was used to analyze the effects on ventricular size and the distribution of stress during infusion. To study regional cerebral autoregulation in patients with possible normal pressure hydrocephalus, a sensitive CBF technique is required that provides absolute, not relative normalized, values for regional CBF and an adequate change in cerebral perfusion pressure must be provoked.
    Journal of Cerebral Blood Flow & Metabolism 06/2004; 24(5):579-87. DOI:10.1097/00004647-200405000-00012 · 5.41 Impact Factor
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    ABSTRACT: The mean cerebral blood flow (CBF) has generally been demonstrated to be lower in normal pressure hydrocephalus (NPH) than in normal controls. We investigated the distribution of the regional peri- and paraventricular white matter CBF (WM CBF) in NPH at baseline and during a controlled rise in intracranial pressure (ICP). Twelve patients with idiopathic NPH (mean age 69 years) underwent a CSF infusion study. CBF was measured by H2(15)O PET at baseline and then during the steady-state plateau of raised ICP. The PET images were co-registered and resliced to 3D structural T1-weighted MRIs. Ten healthy normal volunteers served as control subjects for baseline CBF determination only. Profiles of the regional distribution of the baseline WM CBF and of the percentage change in WM CBF as a function of distance from the ventricles were plotted. The global mean baseline CBF in patients (28.4 +/- 5.2 ml/100 ml/min) was lower than in the control subjects (33 +/- 5.4 ml/100 ml/min) (P < 0.005). In patients, the profile of the regional WM CBF at baseline showed an increase with distance from the ventricles (P < 0.0001), with a maximal reduction adjacent to the ventricles and progressive normalization with distance, whereas in controls no relationship was apparent (P = 0.0748). In 10 patients, the rise in ICP during the infusion produced a fall in cerebral perfusion pressure (CPP) and a significant decrease of the global mean CBF from 27.6 +/- 3.1 to 24.5 +/- 2.9 ml/100 ml/min (P < 0.0001). The profile of the percentage changes in regional WM CBF in patients showed a U-shaped relationship with distance from the ventricles (P = 0.0007), with a maximal decrease skewed on the side of the lateral ventricles at around a mean distance of 9 mm. The WM CBF is reduced in NPH, with an abnormal gradient from the lateral ventricles towards the subcortical WM. An excessive decrease in CBF is brought about by reductions in CPP and appears to be maximal in the paraventricular watershed region. These results are discussed in the light of previous hypotheses concerning the aetiology of periventricular CBF reduction in NPH.
    Brain 05/2004; 127(Pt 5):965-72. DOI:10.1093/brain/awh131 · 9.20 Impact Factor
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    ABSTRACT: Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission tomography and anatomic region-of-interest analysis on co-registered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.
    Journal of Cerebral Blood Flow & Metabolism 02/2004; 24(1):17-23. DOI:10.1097/01.WCB.0000093326.88757.49 · 5.41 Impact Factor

  • 29th International Stroke Conference; 01/2004
  • T Donovan · T D Fryer · A Peña · C Watts · TA Carpenter · J D Pickard ·
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    ABSTRACT: The purpose of this study was to assess the accuracy of high field (3 Tesla) MR in target localization for stem cell transplantation. Three patients with Huntington's disease were imaged with a stereotactic frame in place for both MRI and CT. Quality assurance procedures and manual shimming were performed before each MRI study to minimize image distortion. The images were fused using multi-modality rigid body image registration software. Image fusion demonstrated the MR images to be in agreement with CT to within 1.5 mm, as assessed by measuring the coordinates of markers on the frame and on the shape and size of the lateral ventricles. Target coordinates for transplantation were selected from the MR images. Postoperative imaging confirmed accurate graft placement.
    British Journal of Neurosurgery 11/2003; 17(5):443-9. DOI:10.1080/02688690310001613844 · 0.96 Impact Factor

Publication Stats

980 Citations
89.81 Total Impact Points


  • 1999-2012
    • University of Cambridge
      • • Department of Clinical Neurosciences
      • • Neurosurgery Unit
      • • School of Clinical Medicine
      • • Wolfson Brain Imaging Centre
      • • Department of Radiology
      • • Department of Engineering
      Cambridge, England, United Kingdom