Different patterns of white matter degeneration using multiple diffusion indices and volumetric data in mild cognitive impairment and Alzheimer patients

Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia

Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer's disease

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa

Microstructural damage of the posterior corpus callosum contributes to the clinical severity of neglect

One theory to account for neglect symptoms in patients with right focal damage invokes a release of inhibition of the right parietal cortex over the left parieto-frontal circuits, by disconnection mechanism. This theory is supported by transcranial magnetic stimulation studies showing the existence of asymmetric inhibitory interactions between the left and right posterior parietal cortex, with a right hemispheric advantage. These inhibitory mechanisms are mediated by direct transcallosal projections located in the posterior portions of the corpus callosum. The current study, using diffusion imaging and tract-based spatial statistics (TBSS), aims at assessing, in a data-driven fashion, the contribution of structural disconnection between hemispheres in determining the presence and severity of neglect. Eleven patients with right acute stroke and 11 healthy matched controls underwent MRI at 3T, including diffusion imaging, and T1-weighted volumes. TBSS was modified to account for the presence of the lesion and used to assess the presence and extension of changes in diffusion indices of microscopic white matter integrity in the left hemisphere of patients compared to controls, and to investigate, by correlation analysis, whether this damage might account for the presence and severity of patients' neglect, as assessed by the Behavioural Inattention Test (BIT). None of the patients had any macroscopic abnormality in the left hemisphere; however, 3 cases were discarded due to image artefacts in the MRI data. Conversely, TBSS analysis revealed widespread changes in diffusion indices in most of their left hemisphere tracts, with a predominant involvement of the corpus callosum and its projections on the parietal white matter. A region of association between patients' scores at BIT and brain FA values was found in the posterior part of the corpus callosum. This study strongly supports the hypothesis of a major role of structural disconnection between the right and left parietal cortex in determining 'neglect'

Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome.

22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk

Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia.

Reduced fractional anisotropy (FA) is a well-established correlate of schizophrenia, but it remains unclear whether these tensor-based differences are the result of axon damage and/or organizational changes and whether the changes are progressive in the adult course of illness. Diffusion MRI data were collected in 81 schizophrenia patients (54 first episode and 27 chronic) and 64 controls. Analysis of FA was combined with "fixel-based" analysis, the latter of which leverages connectivity and crossing-fiber information to assess both fiber bundle density and organizational complexity (i.e., presence and magnitude of off-axis diffusion signal). Compared with controls, patients with schizophrenia displayed clusters of significantly lower FA in the bilateral frontal lobes, right dorsal centrum semiovale, and the left anterior limb of the internal capsule. All FA-based group differences overlapped substantially with regions containing complex fiber architecture. FA within these clusters was positively correlated with principal axis fiber density, but inversely correlated with both secondary/tertiary axis fiber density and voxel-wise fiber complexity. Crossing fiber complexity had the strongest (inverse) association with FA (r = -0.82). When crossing fiber structure was modeled in the MRtrix fixel-based analysis pipeline, patients exhibited significantly lower fiber density compared to controls in the dorsal and posterior corpus callosum (central, postcentral, and forceps major). Findings of lower FA in patients with schizophrenia likely reflect two inversely related signals: reduced density of principal axis fiber tracts and increased off-axis diffusion sources. Whereas the former confirms at least some regions where myelin and or/axon count are lower in schizophrenia, the latter indicates that the FA signal from principal axis fiber coherence is broadly contaminated by macrostructural complexity, and therefore does not necessarily reflect microstructural group differences. These results underline the need to move beyond tensor-based models in favor of acquisition and analysis techniques that can help disambiguate different sources of white matter disruptions associated with schizophrenia

A diffusion tensor imaging study of age-related changes in the white matter structural integrity in a common chimpanzee

Diffusion Tensor Magnetic Resonance Imaging was used to examine the age-related changes in white matter structural integrity in the common chimpanzee. Fractional Anisotropy(FA), a measure derived from the diffusion tensor data is sensitive to developmental and pathological changes in axonal density, myelination, size and coherence of organization of fibers within a voxel and thus reflects the white matter structural integrity. There is substantial evidence that white matter structural integrity decreases with age in humans. The long-term goal of this study is to compare the age-related changes in the white matter structural integrity among humans and chimpanzess to provide potential insights into the unique features of human aging. Different methods, including Region Of Interest (ROI) analysis, Tract Based Spatial Statistics (TBSS) are used to describe age-related changes in FA in a group of 21 chimpanzees. Strengths and limitations of these methods were discussed.M.S.Committee Chair: James K. Rilling; Committee Chair: Xiaoping Hu; Committee Member: Shella Keilholz; Committee Member: Todd M. Preus

Progression of microstructural damage in spinocerebellar Ataxia Type 2: A longitudinal DTI study

BACKGROUND AND PURPOSE: The ability of DTI to track the progression of microstructural damage in patients with inherited ataxias has not been explored so far. We performed a longitudinal DTI study in patients with spinocerebellar ataxia type 2. MATERIALS AND METHODS: Ten patients with spinocerebellar ataxia type 2 and 16 healthy age-matched controls were examined twice with DTI (mean time between scans, 3.6 years [patients] and 3.3 years [controls]) on the same 1.5T MR scanner. Using tract-based spatial statistics, we analyzed changes in DTI-derived indices: mean diffusivity, axial diffusivity, radial diffusivity, fractional anisotropy, and mode of anisotropy. RESULTS: At baseline, the patients with spinocerebellar ataxia type 2, as compared with controls, showed numerous WM tracts with significantly increased mean diffusivity, axial diffusivity, and radial diffusivity and decreased fractional anisotropy and mode of anisotropy in the brain stem, cerebellar peduncles, cerebellum, cerebral hemisphere WM, corpus callosum, and thalami. Longitudinal analysis revealed changes in axial diffusivity and mode of anisotropy in patients with spinocerebellar ataxia type 2 that were significantly different than those in the controls. In patients with spinocerebellar ataxia type 2, axial diffusivity was increased in WM tracts of the right cerebral hemisphere and the corpus callosum, and the mode of anisotropy was extensively decreased in hemispheric cerebral WM, corpus callosum, internal capsules, cerebral peduncles, pons and left cerebellar peduncles, and WM of the left paramedian vermis. There was no correlation between the progression of changes in DTI-derived indices and clinical deterioration. CONCLUSIONS: DTI can reveal the progression of microstructural damage of WM fibers in the brains of patients with spinocerebellar ataxia type 2, and mode of anisotropy seems particularly sensitive to such changes. These results support the potential of DTI-derived indices as biomarkers of disease progression

Integration of multi-shell diffusion imaging derived metrics in tractography reconstructions of clinical data

Tese de mestrado integrado Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica), Universidade de Lisboa, Faculdade de Ciências, 2019Nos últimos anos, com o rápido avanço das técnicas imagiológicas, a oportunidade de mapear o cérebro humano in vivo com uma resolução sem precedentes tornou-se realidade, permanecendo ainda hoje como uma das áreas de maior interesse da neurociência. Sabendo que o movimento natural das moléculas de água nos tecidos biológicos é altamente influenciado pelo ambiente microestrutural envolvente, e que a anisotropia que este processo aleatório assume na matéria branca pode ser explorada com o intuito de inferir características importantes associadas ao tecido neuronal, a ressonância magnética ponderada por difusão (dMRI, do inglês “Diffusion-Weighted Magnetic Resonance Imaging") afirmou-se como a técnica de imagem mais amplamente utilizada para a investigação in vivo e não invasiva da conectividade cerebral. A primeira técnica padrão de dMRI foi a imagiologia por tensor de difusão (DTI, do inglês "Diffusion Tensor Imaging"). Implementada com a capacidade de fornecer sensibilidade à microestrutura do tecido, esta técnica permite extrair informação acerca da tridimensionalidade da distribuição da difusão de moléculas de água através da aplicação de seis gradientes de difusão não colineares entre si. Além da difusividade média (MD, do inglês "Mean Diffusivity"), é também possível extrair outros índices microestruturais, como a anisotropia fraccional (FA, do inglês "Fractional Anisotropy"), que fornece informação acerca da percentagem de difusão anisotrópica num determinado voxel. Ambas as métricas são amplamente utilizadas como medidas de alterações microestruturais, todavia, apesar da sua sensibilidade, estes marcadores não são específicos quanto às características individuais da microestrutura tecidual. Regiões com reduzida FA podem camuflar regiões de conformação de cruzamento de fibras, ou fibras muito anguladas, que a DTI não consegue resolver. A razão para esta limitação reside no número reduzido de diferentes direções de difusão que são exploradas, assim como no pressuposto de que a distribuição das moléculas de água é gaussiana, o que não é necessariamente verdade. De forma alternativa e com o intuito de tais limitações serem ultrapassadas, é possível implementar uma representação matemática do sinal adquirido de forma a explorar o propagador de difusão, da qual a imagiologia por ressonância magnética do propagador aparente médio (MAP-MRI, do inglês “Mean Apparent Propagator Magnetic Resonance Imaging”) é exemplo. Esta técnica analítica caracteriza-se pelo cálculo da função de densidade de probabilidade associada ao deslocamento de spin, o que permite descrever o caráter não-gaussiano do processo de difusão tridimensional e quantificar índices escalares inerentes ao processo de difusão, os quais sublinham as características complexas intrínsecas à microestrutura do tecido. Estes parâmetros incluem o deslocamento médio quadrático (MSD, em inglês “mean square displacement”), a probabilidade de retorno à origem (RTOP, do inglês “return-to-the origin probability”) e suas variantes de difusão em uma e duas dimensões – a probabilidade de retorno ao plano (RTPP, do inglês “return-to-the plane probability”) e a probabilidade de retorno ao eixo (RTAP, do inglês “return-to-the axis probability”), respetivamente. Em resposta às limitações da DTI associadas à falta de especificidade para distinguir características microestruturais dos tecidos, surgiu ainda o modelo de Dispersão de Orientação de Neurite e Imagem de Densidade (NODDI, do inglês “Neurite Orientation Dispersion and Density Imaging”), o qual utiliza o processo de difusão para estimar a morfologia das neurites. Tendo como premissa subjacente que o sinal de difusão pode ser definido pela soma da contribuição dos sinais de diferentes compartimentos, este modelo biofísico diferencia o espaço intra e extracelular o que, por sua vez, permite quantificar a dispersão e densidade das neurites. Deste modo, dois parâmetros intrínsecos à microestrutura envolvente podem ser calculados: a densidade neurítica e o índice de dispersão da orientação das neurites. No entanto, de forma a garantir a viabilidade clínica do modelo, este pode ser aplicado por meio do método AMICO (do inglês “Accelerated Microstructure Imaging via Convex Optimization”) através do seu ajuste linear, o que permite o cálculo do índice de dispersão da orientação das neurites (ODI, do inglês “Orientation Dispersion Index”), da fração de volume intracelular (ICVF do inglês, “Intracellular Volume Fraction”), e da fração de volume isotrópico (ISOVF, do inglês “Isotropic Volume Fraction”). O estudo da configuração arquitetural das estruturas cerebrais in vivo, por meio da dMRI associada aos métodos de tractografia, permitiu a reconstrução não invasiva das fibras neuronais e a exploração da informação direcional inerente às mesmas, sendo que o seu estudo tem revelado uma enorme expansão por meio do estabelecimento de marcadores biológicos perante a presença de diversas condições patológicas. O objetivo principal desta dissertação prende-se com existência de uma variação proeminentenas métricas de difusão ao longo dos tratos de matéria branca no cérebro humano. Atualmente, a maioriados estudos de tractografia tem por base uma abordagem que se resume à análise do valor escalar médio da métrica de difusão para a estrutura cerebral em estudo, pelo que se tem verificado um crescente interesse na utilização de métodos que considerem a extensão da variabilidade nas métricas de difusão ao longo dos tratos de modo a providenciarem um maior nível de detalhe ao nível do processo de difusão, evitando interpretações erróneas dos parâmetros microestruturais. Desta forma, em primeiro lugar, foi desenvolvido uma análise ao longo dos tratos de matéria branca, tendo por base a variação dos valores assumidos pelos parâmetros microestruturais acima mencionados. No presente estudo foi possível demonstrar a eficácia de tal abordagem ao longo de três tratos de matéria de branca (fascículo arqueado, trato corticoespinhal, e corpo caloso), para além de permitir, através da variância assumida pelos diversos parâmetros microestruturais, o estudo detalhado de regiões anatómicas que assumem uma distribuição complexa de múltiplos conjuntos populacionais de fibras, como é o caso do centro semioval, o qual constitui uma região de cruzamento de fibras provenientes dos três tratos de matéria branca em estudo. De seguida, esta técnica foi utilizada com sucesso na identificação de diferenças microestruturais por meio do estudo dos diversos parâmetros de difusão em pacientes com diagnóstico prévio de epilepsia no lobo temporal (TLE, do inglês “Temporal Lobe Epilepsy”), com foco epiléptico localizado no hemisfério esquerdo, e controlos. O estudo do ambiente microestrutural por meio dos múltiplos mapas escalares permitiu averiguar a alteração do processo de difusão e/ou anisotropia, associadas ao efeito fisiopatológico da TLE na organização da matéria branca. Os resultados revelaram diferenças localizadas, as quais se traduziram num aumento da difusividade e redução da anisotropia do processo de difusão ao longo dos tratos em estudo dos pacientes com TLE, sugerindo deste modo uma perda na organização das diversas estruturas anatómicas e a expansão do espaço extracelular face aos controlos. Verificou-se ainda que pacientes com esta condição neurológica sofrem de alterações microestruturais que afetam redes cerebrais em grande escala, envolvendo regiões temporais e extratemporais de ambos os hemisférios. Adicionalmente, aplicada como técnica capaz de investigar padrões de mudança na matéria branca, procedeu-se à realização de um estudo assente na estatística espacial baseada no trato (TBSS, do inglês “Tract-Based Spatial Statistics”). Após a exploração das diversas métricas de difusão, os pacientes com TLE (com lateralização à esquerda) demonstraram alterações no processo de difusão, ilustradas pelos diversos padrões de mudança microestrutural de cada métrica em estudo, concordantes com os resultados anteriormente aferidos pela análise ao longo do trato. Por fim, uma análise baseada em fixel (FBA, do inglês “Fixel-Based Analysis”) foi realizada, a qual permitiu uma análise estatística abrangente de medidas quantitativas da matéria branca, com o intuito de detetar alterações no volume intra-axonal por variação na densidade intra-voxel e/ou reorganização da morfologia macroscópica. Para identificar tais diferenças entre pacientes e controlos, três parâmetros foram considerados: densidade das fibras (FD, do inglês “Fibre Density”), seção transversal do feixe de fibras (FC, do inglês “Fibre-bundle Cross-section”), e densidade de fibras e seção transversal (FDC, do inglês “Fibre Density and Cross-section). Reduções na FD, FC e FDC foram identificadas em pacientes com TLE (com lateralização à esquerda) em comparação com os controlos, o que está de acordo com as mudanças microestruturais que resultam do processo de degeneração que afeta as estruturas de matéria branca com a perda de axónios na presença de uma condição neuropatológica como a TLE. Apesar do resultado final positivo, tendo em conta a meta previamente estabelecida, está aberto o caminho para o seu aperfeiçoamento, tendo em vista as direções futuras que emergem naturalmente desta dissertação. Como exemplo disso, poder-se-á recorrer ao estudo pormenorizado das metodologias técnicas associadas à abordagem apresentada que tem por base a análise das métricas de difusão ao longo dos tratos de matéria branca, uma vez que o desvio padrão associado a cada valor atribuído pelas diversas métricas foi significativo, o que de alguma forma poderá ter influenciado os resultados e, consequentemente, as conclusões deles extraídas, tendo em vista a sua viabilidade enquanto aplicação clínica. Como nota final, gostaria apenas de salientar que a imagiologia por difusão e, em particular, a tractografia têm ainda muito espaço para progredir. A veracidade desta afirmação traduz-se pela existência de uma grande variedade de modelos e algoritmos implementados, bem como de técnicas e metodologias de análise à informação microestrutural retida tendo por base o perfil de difusão que carateriza cada trato em estudo, sem que no entanto, exista consenso na comunidade científica acerca da melhor abordagem a seguir.Diffusion-weighted magnetic resonance imaging (dMRI) is a non-invasive imaging method which has been successfully applied to study white matter (WM) in order to determine physiological information and infer tissue microstructure. The human body is filled with barriers affecting the mobility of molecules and preventing it from being constant in different directions (anisotropic diffusion). In the brain, the sources for this anisotropy arise from dense packing axons and from the myelin sheath that surrounds them. Diffusion Tensor Imaging (DTI) is widely used to extract fibre directions from diffusion data, but it fails in regions containing multiple fibre orientations. The constrained spherical deconvolution technique had been proposed to address this limitation. It provides an estimate of the fibre orientation distribution that is robust to noise whilst preserving angular resolution. As a noninvasive technique that generates a three-dimensional reconstruction of neuronal fibres, tractography is able to map in vivo the human WM based on the reconstruct of the fibre orientations from the diffusion profile. Most of the tractography studies use a “tract-averaged” approach to analysis, however it is well known that there is a prominent variation in diffusion metrics within WM tracts. In this study we address the challenge of defining a microstructural signature taking into account the potentially rich anatomical variation in diffusion metrics along the tracts. Therefore, a workflow to conduct along-tract analysis of WM tracts (namely, arcuate fasciculus, corticospinal and corpus callosum) and integrate not only DTI derived measures, but also more advanced parameters from Mean Apparent Propagator-Magnetic Resonance Imaging (MAP-MRI) and Neurite Orientation Dispersion and Density Imaging (NODDI) model, was developed across healthy controls and patients with Temporal Lobe Epilepsy (TLE). Beyond the true biological variation in diffusion properties along tracts, this technique was applied to show that it allows a more detailed analysis of small regions-of-interest extracted from the tract in order to avoid fibres from WM pathways in the neighbourhood, which might lead to equivocal biological interpretations of the microstructural parameters. Consequently, the along-tract streamline distribution from the centrum semiovale, which is known to be a complex fibre geometry with multiple fibres populations from arcuate fasciculus, corticospinal and corpus callosum, was investigated. Finally, to validate our approach and highlight the strength of this extensible framework, two other methods were implemented in order to support the conclusions derived from the along-tract analysis computed between-groups. Firstly, a tract-based spatial statistics (TBSS) analysis was performed to study the WM change patterns across the whole brain in patients with TLE, and explore the alteration of multiple diffusion metrics. This voxel-based technique provides a powerful and objective method to perform multi-subject comparison, based on voxel-wise statistics of diffusion metrics but simultaneous aiming to minimize the effects of misalignment using a conventional voxel-based analysis method. With this in mind, the results showed increased diffusivity and reduced diffusion anisotropy, suggesting a loss of structural organization and expansion of the extracellular space in the presence of neuropathological condition as TLE. Secondly, the fixel-based analysis (FBA) was performed allowing a comprehensive statistical analysis of WM quantitative measures in order to have access to changes that may result within WM tracts in the presence of TLE. The microstructural/macrostructural changes in WM tracts of TLE patients were observed in temporal and extratemporal regions of both hemispheres, which agrees with the concept that epilepsy is a network disorder

Obrazowanie tensora dyfuzji u pacjentów z chorobą Alzheimera i łagodnymi zaburzeniami poznawczymi

A wide range of imaging studies provides growing support for the potential role of diffusion tensor imaging (DTI) in evaluating microstructural white matter integrity in Alzheimer disease (AD) and mild cognitive impairment (MCI). Our review aims to present DTI principles, post-processing and analysis frameworks and to report the results of particular studies. The distribution of AD-related white matter abnormalities is widely discussed in the light of deteriorated connectivity within certain tracts due to secondary white matter degeneration; primary alterations are also assumed to contribute to the pattern. The question whether it is more effective to assess the whole-brain diffusion or to directly concentrate on specific regions remains an interesting issue. Assessing white matter microstructure alterations, as evaluated by group-level differences of tensor-derived parameters, may be a promising neuroimaging tool for differential diagnosis between AD, MCI and other cognitive disorders, as well as being particularly helpful in the interpretation of underlying pathological processes.Rosnąca liczba badań naukowych wskazuje na znaczenie obrazowania tensora dyfuzji (DTI) w ocenie mikrostrukturalnej integralności istoty białej w chorobie Alzheimera (ChA) i łagodnych zaburzeniach poznawczych (ŁZP). W niniejszej pracy przeglądowej omówiono zasady obróbki danych oraz analizy DTI i przedstawiono wyniki poszczególnych badań prezentujących różne modele charakterystycznych dla ChA zmian w istocie białej. Szeroko dyskutowane jest rozmieszczenie uszkodzeń w istocie białej, głównie w odniesieniu do wtórnego zwyrodnienia poszczególnych włókien wskutek zaniku istoty szarej lub pierwotnego zwyrodnienia istoty białej. Interesujący i nierozstrzygnięty pozostaje dylemat, czy bardziej efektywne jest obrazowanie zmian dyfuzji w całym mózgu, czy skupianie się na konkretnych strukturach. Zastosowanie DTI w ocenie mikrostrukturalnych zmian zachodzących w istocie białej mózgu może być obiecującym narzędziem w różnicowaniu pomiędzy ChA, ŁZP i innymi zaburzeniami poznawczymi; jest szczególnie przydatne przy interpretacji leżących u ich podłoża procesów patologicznych