EDUARDO JOAQUIM LOPES ALHO
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- Magnetic resonance diffusion tensor imaging for the pedunculopontine nucleus: proof of concept and histological correlation(2017) ALHO, A. T. D. L.; HAMANI, C.; ALHO, E. J. L.; SILVA, R. E. da; SANTOS, G. A. B.; NEVES, R. C.; CARREIRA, L. L.; ARAUJO, C. M. M.; MAGALHAES, G.; COELHO, D. B.; ALEGRO, M. C.; MARTIN, M. G. M.; GRINBERG, L. T.; PASQUALUCCI, C. A.; HEINSEN, H.; FONOFF, E. T.; AMARO JR., E.The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ postmortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10 mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.
- Use of computational fluid dynamics for 3D fiber tract visualization on human high-thickness histological slices: histological mesh tractography(2021) ALHO, Eduardo Joaquim Lopes; FONOFF, Erich T.; ALHO, Ana Tereza Di Lorenzo; NAGY, Jozsef; HEINSEN, HelmutUnderstanding the intricate three-dimensional relationship between fiber bundles and subcortical nuclei is not a simple task. It is of paramount importance in neurosciences, especially in the field of functional neurosurgery. The current methods for in vivo and post mortem fiber tract visualization have shortcomings and contributions to the field are welcome. Several tracts were chosen to implement a new technique to help visualization of white matter tracts, using high-thickness histology and dark field images. Our study describes the use of computational fluid dynamic simulations for visualization of 3D fiber tracts segmented from dark field microscopy in high-thickness histological slices (histological mesh tractography). A post mortem human brain was MRI scanned prior to skull extraction, histologically processed and serially cut at 430 mu m thickness as previously described by our group. High-resolution dark field images were used to segment the outlines of the structures. These outlines served as basis for the construction of a 3D structured mesh, were a Finite Volume Method (FVM) simulation of water flow was performed to generate streamlines representing the geometry. The simulations were accomplished by an open source computer fluid dynamics software. The resulting simulation rendered a realistic 3D impression of the segmented anterior commissure, the left anterior limb of the internal capsule, the left uncinate fascicle, and the dentato-rubral tracts. The results are in line with clinical findings, diffusion MR imaging and anatomical dissection methods.
- Lateral hypothalamic activity indicates hunger and satiety states in humans(2017) TALAKOUB, Omid; PAIVA, Raquel R.; MILOSEVIC, Matija; HOEXTER, Marcelo Q.; FRANCO, Ruth; ALHO, Eduardo; NAVARRO, Jessie; PEREIRA JR., Jose F.; POPOVIC, Milos R.; SAVAGE, Cary; LOPES, Antonio C.; ALVARENGA, Pedro; DAMIANI, Durval; TEIXEIRA, Manoel J.; MIGUEL, Euripides C.; FONOFF, Erich T.; BATISTUZZO, Marcelo C.; HAMANI, ClementLateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader-Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food-related cues induced an increase in beta/low-gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, we have delivered alpha-frequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity.
- Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala's nucleus(2014) TEIPEL, Stefan J.; FLATZ, Wilhelm; ACKL, Nibal; GROTHE, Michel; KILIMANN, Ingo; BOKDE, Arun L. W.; GRINBERG, Lea; AMARO JR., Edson; KLJAJEVIC, Vanja; ALHO, Eduardo; KNELS, Christina; EBERT, Anne; HEINSEN, Helmut; DANEK, AdrianPrimary progressive aphasia (PPA) is characterized by left hemispheric frontotemporal cortical atrophy. Evidence from anatomical studies suggests that the nucleus subputaminalis (NSP), a subnucleus of the cholinergic basal forebrain, may be involved in the pathological process of PPA. Therefore, we studied the pattern of cortical and basal forebrain atrophy in 10 patients with a clinical diagnosis of PPA and 18 healthy age matched controls using high resolution magnetic resonance imaging (MRI). We determined the cholinergic basal forebrain nuclei according to Mesulam's nomenclature and the NSP in MRI reference space based on histological sections and the MRI scan of a post-mortem brain in cranio. Using voxel-based analysis, we found left hemispheric cortical atrophy in PPA patients compared with controls, including prefrontal, lateral temporal and medial temporal lobe areas. We detected cholinergic basal forebrain atrophy in left predominant localizations of Ch4p, Ch4am, Ch4al, Ch3 and NSP. For the first time, we have described the pattern of basal forebrain atrophy in PPA and confirmed the involvement of NSP that had been predicted based on theoretical considerations. Our findings may enhance understanding of the role of cholinergic degeneration for the regional specificity of the cortical destruction leading to the syndrome of PPA.
- Peduncolopontine DBS improves balance in progressive supranuclear palsy: Instrumental analysis(2016) SOUZA, Carolina de Oliveira; LIMA-PARDINI, Andrea Cristina de; COELHO, Daniel Boari; MACHADO, Rachael Brant; ALHO, Eduardo Joaquim Lopes; ALHO, Ana Tereza Di Lorenzo; TEIXEIRA, Luis Augusto; TEIXEIRA, Manoel Jacobsen; BARBOSA, Egberto Reis; FONOFF, Erich Talamoni
- Training with brain-machine interfaces, visuotactile feedback and assisted locomotion improves sensorimotor, visceral, and psychological signs in chronic paraplegic patients(2018) SHOKUR, Solaiman; DONATI, Ana R. C.; CAMPOS, Debora S. F.; GITTI, Claudia; BAO, Guillaume; FISCHER, Dora; ALMEIDA, Sabrina; BRAGA, Vania A. S.; AUGUSTO, Patricia; PETTY, Chris; ALHO, Eduardo J. L.; LEBEDEV, Mikhail; SONG, Allen W.; NICOLELIS, Miguel A. L.Spinal cord injury (SCI) induces severe deficiencies in sensory-motor and autonomic functions and has a significant negative impact on patients' quality of life. There is currently no systematic rehabilitation technique assuring recovery of the neurological impairments caused by a complete SCI. Here, we report significant clinical improvement in a group of seven chronic SCI patients (six AIS A, one AIS B) following a 28-month, multi-step protocol that combined training with non-invasive brain-machine interfaces, visuo-tactile feedback and assisted locomotion. All patients recovered significant levels of nociceptive sensation below their original SCI (up to 16 dermatomes, average 11 dermatomes), voluntary motor functions (lower-limbs muscle contractions plus multi-joint movements) and partial sensory function for several modalities (proprioception, tactile, pressure, vibration). Patients also recovered partial intestinal, urinary and sexual functions. By the end of the protocol, all patients had their AIS classification upgraded (six from AIS A to C, one from B to C). These improvements translated into significant changes in the patients' quality of life as measured by standardized psychological instruments. Reexamination of one patient that discontinued the protocol after 12 months of training showed that the 16-month break resulted in neurological stagnation and no reclassification. We suggest that our neurorehabilitation protocol, based uniquely on non-invasive technology (therefore necessitating no surgical operation), can become a promising therapy for patients diagnosed with severe paraplegia (AIS A, B), even at the chronic phase of their lesion.
- High thickness histological sections as alternative to study the three-dimensional microscopic human sub-cortical neuroanatomy(2018) ALHO, Eduardo Joaquim Lopes; ALHO, Ana Tereza Di Lorenzo; GRINBERG, Lea; AMARO JR., Edson; SANTOS, Glaucia Aparecida Bento dos; SILVA, Rafael Emidio da; NEVES, Ricardo Caires; ALEGRO, Maryana; COELHO, Daniel Boari; TEIXEIRA, Manoel Jacobsen; FONOFF, Erich Talamoni; HEINSEN, HelmutStereotaxy is based on the precise image-guided spatial localization of targets within the human brain. Even with the recent advances in MRI technology, histological examination renders different (and complementary) information of the nervous tissue. Although several maps have been selected as a basis for correlating imaging results with the anatomical locations of sub-cortical structures, technical limitations interfere in a point-to-point correlation between imaging and anatomy due to the lack of precise correction for post-mortem tissue deformations caused by tissue fixation and processing. We present an alternative method to parcellate human brain cytoarchitectural regions, minimizing deformations caused by post-mortem and tissue-processing artifacts and enhancing segmentation by means of modified high thickness histological techniques and registration with MRI of the same specimen and into MNI space (ICBM152). A three-dimensional (3D) histological atlas of the human thalamus, basal ganglia, and basal forebrain cholinergic system is displayed. Structure's segmentations were performed in high-resolution dark-field and light-field microscopy. Bidimensional non-linear registration of the histological slices was followed by 3D registration with in situ MRI of the same subject. Manual and automated registration procedures were adopted and compared. To evaluate the quality of the registration procedures, Dice similarity coefficient and normalized weighted spectral distance were calculated and the results indicate good overlap between registered volumes and a small shape difference between them in both manual and automated registration methods. High thickness high-resolution histological slices in combination with registration to in situ MRI of the same subject provide an effective alternative method to study nuclear boundaries in the human brain, enhancing segmentation and demanding less resources and time for tissue processing than traditional methods.
bookPart Neurocirurgia(2023) MONACO, Bernardo A. de; ALHO, Eduardo J. L.; BRANCO, Luis Castelo- Deep brain stimulation modulates hypothalamic-brainstem fibers in cluster headache: case report(2020) DANTAS, Sergio A. F.; ALHO, Eduardo J. L.; SILVA, Juliano J. da; MENDES NETO, Nilson N.; FONOFF, Erich Talamoni; HAMANI, ClementHypothalamic deep brain stimulation (DBS) has been used for more than a decade to treat cluster headache (CH) but its mechanisms remain poorly understood. The authors have successfully treated a patient with CH using hypothalamic DBS and found that the contact used for chronic stimulation was located in a white matter region posterior to the mammillary bodies. Fiber tracts crossing that region were the medial forebrain bundle and those interconnecting the hypothalamus and brainstem, including the dorsal longitudinal fasciculus. Because the stimulation of axons is an important mechanism of DBS, some of its clinical effects in CH may be related to the stimulation of fibers interconnecting the hypothalamus and brainstem.
- High-resolution resources and histological mesh tractography(2021) ALHO, E. J. L.; FONOFF, E. T.; HEINSEN, H.Histological techniques have been developed since the 17th century, aiming to understand the microscopic features of biological tissues. Almost 350 years later, the human brain has still its secrets, but several tools were developed to unravel them. In this chapter, we will discuss how high-resolution resources, such as histology, can help us to add new details to complete the human brain connectivity puzzle. Special focus will be given to histological mesh tractography, a newly proposed method that helps three-dimensional visualization of fiber tracts derived from high-resolution histological images, in the context of deep brain stimulation. © 2022 Elsevier Inc. All rights reserved.