Fig 4 - uploaded by Hosung Kim
Content may be subject to copyright.
Analysis of the left hippocampus in left TLE. (a) Four hippocampi (superior and inferior views) of TLE patients aligned to a template built from 33 control subjects. The template is shown in transparent red. The patients’ hippocampi are in solid blue (purple shows areas of overlap with the template). (b) Signed surface-normal component maps of the displacement vectors (SNV; color scale in mm, -/+ signs indicate inward/outward deformation). Paired black arrows indicate the region where a local shifting/bending is detected. These changes at the level of the hippocampal tail are clearly visible in (a). (c) Surface-based Jacobian determinant maps (SJD; color scale in mm 3 , -/+ signs indicate volume loss/growth).
Source publication
Analysis of surface-based displacement vectors using spherical harmonic description (SPHARM) localizes shape changes accurately. However, it does not allow differentiating volume variations from shifting and/or bending. We propose a new approach to quantify local volume changes by computing the surface-based Jacobian determinant. This measurement i...
Contexts in source publication
Context 1
... differences were assessed by vertex-wise t-tests with correction for multiple comparisons using FDR. In patients, SNV detected areas of inward deformations at the level of hippocampal head and body ipsilateral to the seizure focus, and areas of mirrored inward/outward deformations in the tail due to local shifting (Figure 4-a). There were also areas of subtle focal inward deformation at the level of the contralateral hippocampal body. ...
Similar publications
Background: In multiple sclerosis (MS), brain atrophy quantification is affected by white matter lesions. LEAP and FSL-lesion_filling, replace lesion voxels with white matter intensities; however, they require precise lesion identification on 3DT1-images.
Aim: To determine whether 2DT2 lesion masks co-registered to 3DT1 images, yield grey and white...
Citations
... As labels were created in a stereotaxic space, correction for intracranial volume was not required. A previously validated surface-based approach (Kim et al. 2008) was used to measure local volume changes by computing Jacobian determinants on surface-based displacement vectors between a given subject and a template surface (Styner et al. 2006). Caudate labels were converted to surface meshes using a spherical parameterization (SPHARM) based on area-preserving, distortionminimizing mapping. ...
... Displacement vectors were diffused within the volume enclosed by the surface using a heat equation, yielding a displacement vector field. To assess local volume changes, we calculated Jacobian determinants from these vector fields (Kim et al. 2008). Jacobian determinants were projected back onto the template surface using tri-linear interpolation and subtracting 1, we obtained a metric of growth (J > 0) or shrinkage (J < 0) in a unit-size cube (i.e., voxel) defined on each vertex. ...
In patients with premotor Huntington’s disease (pmHD), literature has reported decreases in caudate volume. However, the regional vulnerability of the caudate nucleus to pmHD remains to be clarified. We aimed to determine whether regional structural damage of the caudate nucleus was present in pmHD and was correlated with clinical profile using a surface-based morphometric technique applied to T1-weighted MRI. The study cohort consisted of 14 volunteers with genetically confirmed pmHD (6 males; 41.8 ± 13.2 years) and 11 age- and sex-matched controls (5 males; 46.2 ± 11.9 years, p > 0.3). On 3-T T1-weighted images, bilateral caudate volumes were manually delineated. The resulting labels were converted to a surface, triangulated with 1002 points equally distributed across subjects using SPHARM-PDM. Displacement vectors were then computed between each individual and a template surface representing the whole cohort. Computing point-wise Jacobian determinants (JD) from these vectors quantified local volumes. We found decreases in bilateral global caudate volumes in the pmHD group compared to controls (t = 3.4; p = 0.002). Point-wise analysis of local volumes mapped caudate atrophy in pmHD primarily onto medial surface (t > 2.7; FDR < 0.05), with most pronounced changes in anteromedial subdivision. In a combined group of patients and controls, volume within the area presenting significant group difference was positively correlated with scores of executive function (r = 0.7; p < 0.001) and working memory (r = 0.6; p = 0.002). In patients, the caudate atrophy was associated with increase in disease burden (r = 0.7; p = 0.005). Caudate subnuclear atrophy measured using our surface-based morphometric technique is evident in pmHD, correlates with clinical variables, and may provide a more sensitive biomarker than global volumes.
... We used a previously validated surface-based approach (Kim et al. 2008) that reliably measured local volume changes of amygdalo-hippocampal structures (Bernhardt et al. 2013;Kim et al. 2013). This approach computes Jacobian determinants on surface-based displacement vectors between a given subject and a template surface (Styner et al. 2006a). ...
... Displacement vectors were diffused within the volume enclosed by the surface using a heat equation, yielding a displacement vector field. To assess local volume changes, we finally calculated Jacobian determinants from these vector fields (Kim et al. 2008). By projecting these Jacobian determinants back onto the surface using tri-linear interpolation and subtracting 1 from them, we obtained a metric of growth (J>0) or shrinkage (J<0) in a unit-size cube defined on each vertex. ...
Although the role of hypocretin-mediated amygdalo-hippocampal dysfunction is hypothesized to be linked with narcolepsy, there have been no human MRI studies investigating the relationship between their regional volume and key symptoms of narcolepsy. To investigate the morphological changes of amygdalo-hippocampus and its relationship with clinical features in patients with narcolepsy, point-wise morphometry that allowed for measuring the regional volumes of amygdalo-hippocampus on T1-weighted MRI was applied. Participants were 33 drug-naïve patients and 35 age-/gender-matched controls (mean ± SD: 27 ± 6 years). We compared hippocampal and amygdalar subfields volumes between patients and controls and correlated between volume and clinical and neuropsychological features in patients. Bilateral hippocampal atrophy (183 vertices) was identified mainly located within the CA1 subfield (FDR < 0.05). Significant amygdalar volume reduction was found in the areas of the centromedial (102 vertices) and laterobasal nuclear groups (LB, 35 vertices). There was no volume increase in patients relative to controls (FDR >0.2). After controlling depressive mood, sleep quality, age, and gender, hippocampal CA1 atrophy and amygdalar centromedial atrophy were associated with longer duration of daytime sleepiness and shorter mean REM sleep latency (|r| >0.44, p < 0.01). The amygdalar centromedial atrophy was associated with longer duration of cataplexy (|r| >0.47, p < 0.005). Subfields atrophy of amygdalo-hippocampus in untreated patients with narcolepsy that was found relative to controls suggests that CA1 of the hippocampus and centromedial area of amygdala are closely related to the severity of narcolepsy and play a crucial role in the circuitry of cataplexy.
... The signed surface normal components of these vectors quantify inward/ outward deformations. To compute volume changes, we applied the heat equation to interpolate vertex-wise displacement vectors within the volume enclosed by SPHARM-PDM surfaces[Kim et al., 2008]. The Jacobian determinant J of the resulting vector field was projected back onto the surface, quantifying growth (J-1 > 0) or shrinkage (J-1 < 0) in surface-normal direction. ...
... However, it has been pointed out that VBM may cause inaccurate assessment in regions of cortical overlap [17]. Surface-based morphometry is feasible to precisely quantify and characterize the cortical thickness in different regions181920. By using this method, comparison of the cortical thickness in the four lateral occipital regions (the medial lingual cortex, the cuneus, the superior occipital cortex and the lunate cortex) showed that these regions are significantly thinner in amblyopic patients than in controls [7]. ...
Previous studies have indicated regional abnormalities of both gray and white matter in amblyopia. However, alterations of cortical thickness associated with changes in white matter integrity have rarely been reported. In this study, structural magnetic resonance imaging and diffusion tensor imaging (DTI) data were obtained from 15 children with anisometropic amblyopia and 15 age- and gender-matched children with normal sight. Combining DTI and surface-based morphometry, we examined a potential linkage between disrupted white matter integrity and altered cortical thickness. The fractional anisotropy (FA) values in the optic radiations (ORs) of children with anisometropic amblyopia were lower than in controls (P < 0.05). The cortical thickness in amblyopic children was lower than controls in the following subregions: lingual cortex, lateral occipitotemporal gyrus, cuneus, occipital lobe, inferior parietal lobe, and temporal lobe (P < 0.05, corrected), but was higher in the calcarine gyrus (P < 0.05, corrected). Node-by-node correlation analysis of changes in cortical thickness revealed a significant association between a lower FA value in the OR and diminished cortical thickness in the following subregions: medial lingual cortex, lateral occipitotemporal gyrus, lateral, superior, and medial occipital cortex, and lunate cortex. We also found a relationship between changes of cortical thickness and white matter OR integrity in amblyopia. These findings indicate that developmental changes occur simultaneously in the OR and visual cortex in amblyopia, and provide key information on complex damage of brain networks in anisometropic amblyopia. Our results also support the hypothesis that the pathogenesis of anisometropic amblyopia is neurodevelopmental.
... The signed surface normal components of these vectors quantify inward/ outward deformations. To compute volume changes, we applied the heat equation to interpolate vertex-wise displacement vectors within the volume enclosed by SPHARM-PDM surfaces [Kim et al., 2008]. The Jacobian determinant J of the resulting vector field was projected back onto the surface, quantifying growth (J-1 > 0) or shrinkage (J-1 < 0) in surface-normal direction. ...
In drug-resistant temporal lobe epilepsy (TLE), MRI studies have shown consistent mesio- temporal and neocortical structural alterations when comparing patients to healthy controls. It remains, however, relatively unclear whether the side of seizure focus differentially impacts the degree of struc- tural damage. This work performed a comprehensive surface-based analysis of mesiotemporal and neocortical morphology on preoperative 1.5 T MRI in 25/35 LTLE/RTLE patients that achieved seizure freedom after surgery (i.e., Engel-I outcome; 7 6 2 years follow-up), an imaging-independent confirma- tion of focus lateralization. Compared to 46 age- and sex-matched controls, both TLE groups displayed marked ipsilateral atrophy in mesiotemporal regions, while cortical thinning was bilateral. Direct con- trasts between LTLE and RTLE did not reveal significant differences. Bootstrap simulations indicated low reproducibility of observing a between-cohort difference; power analysis revealed that more than 110 patients would be necessary to detect subtle differences. No difference between LTLE and RTLE was confirmed when using voxel-based morphometry, an independent proxy of gray matter volume. Similar results were obtained analyzing a separate 3 T dataset (15/15 LTLE/RTLE patients; Engel-I after 462 years follow-up; 42 controls). Our results strongly support equivalent gray matter compro- mise in left and right TLE. The morphological profile of seizure-free patients, presenting with ipsilat- eral mesiotemporal and bilateral cortical atrophy, motivates the development of neuromarkers of outcome that consider both mesiotemporal and neocortical structures.
... Notwithstanding recent progress in the MRI-based visualization of mesiotemporal lobe internal anatomy on postmortem brains (Adler et al. 2014), the in vivo identification of all subregional borders or subfields within a given structure lies beyond the resolution of clinically feasible exams. We circumvented this challenge by using heuristic boundaries drawn on MRI-derived surface templates instead of defining borders in each individual, a strategy opted in various studies (Hogan et al. 2004;Kim et al. 2008;Bernhardt, Kim et al. 2013). Note that, while this approach is not appropriate for brain structures with subdivisions hidden in the depth, it is conceptually sound to approximate boundaries for those that reach the surface; this is the case for all hippocampal subfields but CA4, all entorhinal subdivisions and all amygdalar nuclei aside from the magnocellular portion of the basal nucleus. ...
... The signed surface-normal components of these vectors quantify inward/outward deformations. To compute pointwise volume changes, we applied a heat propagation approach to interpolate the pointwise displacement vectors within the volume enclosed by the SPHARM-PDM surface (Kim et al. 2008). The Jacobian determinant J of the resulting dense vector field was projected back onto the surface to quantify growth (J−1 > 0) or shrinkage (J−1 < 0) along the surface-normal direction. ...
... The current work, on the other hand, targeted the topology of networks within the assembly of regions forming Cerebral Cortex, 2016, Vol. 26, No. 7 the mesiotemporal circuitry. Notably, while our covariance analysis operated on surface-shape measures of local volume, a surrogate marker of limbic histopathology (Hogan et al. 2004Kim et al. 2008;Bernhardt et al. 2012;Maccotta et al. 2015), these measures were corrected for confounds of global mean atrophy prior to network construction. Our findings, thus, likely reflect topology-level rearrangements in network organization above and beyond effects of global mesiotemporal atrophy. ...
Temporal lobe epilepsy (TLE) is the most frequent drug-resistant epilepsy in adults and commonly associated with variable degrees of mesiotemporal atrophy on magnetic resonance imaging (MRI). Analyses of inter-regional connectivity have unveiled disruptions in large-scale cortico-cortical networks; little is known about the topological organization of the mesiotemporal lobe, the limbic subnetwork central to the disorder. We generated covariance networks based on high-resolution MRI surface-shape descriptors of the hippocampus, entorhinal cortex, and amygdala in 134 TLE patients and 45 age- and sex-matched controls. Graph-theoretical analysis revealed increased path length and clustering in patients, suggesting a shift toward a more regularized arrangement; findings were reproducible after split-half assessment and across 2 parcellation schemes. Analysis of inter-regional correlations and module participation showed increased within-structure covariance, but decreases between structures, particularly with regards to the hippocampus and amygdala. While higher clustering possibly reflects topological consequences of axonal sprouting, decreases in interstructure covariance may be a consequence of disconnection within limbic circuitry. Preoperative network parameters, specifically the segregation of the ipsilateral hippocampus, predicted long-term seizure freedom after surgery.
© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
... 13 The individual surface is then registered to either a group surface or a template, followed by computation of some type of displacement measure at each vertex in relation to the group surface or template. 14,15 Yet this displacement measure often not only captures local shape changes but also includes confounds such as changes in position (mirroring) between the individual surface and the template, although some investigators have minimized this by using nonlinear methods. 15,16 A method invariant to position changes and registration artifacts would thus be attractive. ...
... 14,15 Yet this displacement measure often not only captures local shape changes but also includes confounds such as changes in position (mirroring) between the individual surface and the template, although some investigators have minimized this by using nonlinear methods. 15,16 A method invariant to position changes and registration artifacts would thus be attractive. ...
Hippocampal atrophy in temporal lobe epilepsy (TLE) can indicate mesial temporal sclerosis and predict surgical success. Yet many patients with TLE do not have significant atrophy (magnetic resonance imaging (MRI) negative), which presents a diagnostic challenge. We used a new variant of high-dimensional large-deformation mapping to assess whether patients with apparently normal hippocampi have local shape changes that mirror those of patients with significant hippocampal atrophy.
Forty-seven patients with unilateral TLE and 32 controls underwent structural brain MRI. High-dimensional large-deformation mapping provided hippocampal surface and volume estimates for each participant, dividing patients into low versus high hippocampal atrophy groups. A vertex-level generalized linear model compared local shape changes between groups.
Patients with low-atrophy TLE (MRI negative) had significant local hippocampal shape changes compared to controls, similar to those in the contralateral hippocampus of high-atrophy patients. These changes primarily involved the subicular and hilar/dentate regions, instead of the classically affected CA1 region. Disease duration instead co-varied with lateral hippocampal atrophy, co-localizing with the CA1 subfield.
These findings show that patients with "MRI-negative" TLE have regions of hippocampal atrophy that cluster medially, sparing the lateral regions (CA1) involved in high-atrophy patients. This suggests an overall effect of temporal lobe seizures manifesting as bilateral medial hippocampal atrophy, and a more selective effect of hippocampal seizures leading to disease-proportional CA1 atrophy, potentially reflecting epileptogenesis.
Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
... 37 Furthermore, it computes surface-based, point-wise jacobian determinants that represent local volume changes of a given hippocampus relative to the mean shape of all healthy hippocampi. 38 Compared to conventional surface shape analyses, 23,33 our technique, derived from other approaches, 37,39 allows the measurement of actual changes in volume independent of positional changes. 38,40 ...
... 38 Compared to conventional surface shape analyses, 23,33 our technique, derived from other approaches, 37,39 allows the measurement of actual changes in volume independent of positional changes. 38,40 ...
... To assess local volume changes, we fi nally calculated jacobian determinants from these vector fi elds. 38 By projecting these jacobian determinants back onto the surface using trilinear interpolation and subtracting one from them, we obtained a metric of growth (J > 0) or shrinkage (J < 0) in a unit-size cube defi ned on each vertex ( Figure 2F). We have previously shown that volume change at a vertex is driven by the structure underneath the surface. ...
Study objectives:
Despite compelling evidence from animal studies indicating hippocampal subfield-specific vulnerability to poor sleep quality and related cognitive impairment, there have been no human magnetic resonance imaging (MRI) studies investigating the relationship between hippocampal subfield volume and sleep disturbance. Our aim was to investigate the pattern of volume changes across hippocampal subfields in patients with primary insomnia relative to controls.
Design:
Pointwise morphometry allowed for volume measurements of hippocampal regions on T1-weighted MRI.
Setting:
University hospital.
Patients:
Twenty-seven unmedicated patients (age: 51.2 ± 9.6 y) and 30 good sleepers as controls (50.4 ± 7.1 y).
Interventions:
N/A.
Measurements:
We compared hippocampal subfield volumes between patients and controls and correlated volume with clinical and neuropsychological features in patients.
Results:
Patients exhibited bilateral atrophy across all hippocampal subfields (P < 0.05 corrected). Cornu ammonis (CA) 1 subfield atrophy was associated with worse sleep quality (higher Pittsburgh Sleep Quality Index and higher arousal index of polysomnography) (r < -0.45, P < 0.005). The volume of the combined region, including the dentate gyrus (DG) and CA3-4, negatively correlated with verbal memory, verbal information processing, and verbal fluency in patients (|r| > 0.45, P < 0.05). Hemispheric volume asymmetry of this region (left smaller than right) was associated with impaired verbal domain functions (r = 0.50, P < 0.005).
Conclusion:
Hippocampal subfield atrophy in chronic insomnia suggests reduced neurogenesis in the dentate gyrus (DG) and neuronal loss in the cornu ammonis (CA) subfields in conditions of sleep fragmentation and related chronic stress condition. Atrophy in the CA3-4-DG region was associated with impaired cognitive functions in patients. These observations may provide insight into pathophysiological mechanisms that make patients with chronic sleep disturbance vulnerable to cognitive impairment.
Citation:
Joo EY, Kim H, Suh S, Hong SB. Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry.
... To localize disease progression at a subregional level, we applied our previously developed and validated method based on spherical harmonic shape descriptors. 8 METHODS Subjects. We studied 134 patients referred to our hospital for the investigation of drug-resistant TLE. ...
... We have previously developed and validated a method to localize subregional structural changes. 8 In brief, mesiotemporal labels of the baseline scan were converted to surface meshes and parameterized using spherical harmonics with a point distribution model (SPHARM-PDM). 14 For each mesiotemporal structure, SPHARM-PDM surfaces of each individual were rigidly aligned to a template (constructed from the mean surface of controls and patients) with respect to the centroid and the longitudinal axis of the first-order ellipsoid. ...
... 14 To compute cross-sectional volume changes, we applied the heat equation to interpolate the vertex-wise displacement vectors within the volume enclosed by the SPHARM-PDM surface boundary. 8 The Jacobian determinant of the resulting vector field was projected back onto the surface. By subtracting 1 from the Jacobian determinant, we quantified growth (J . ...
Evidence for disease progression in the mesiotemporal lobe is mainly derived from global volumetry of the hippocampus. In this study, we tracked progressive structural changes in the hippocampus, amygdala, and entorhinal cortex in drug-resistant temporal lobe epilepsy at a subregional level. Furthermore, we evaluated the relation between disease progression and surgical outcome.
We combined cross-sectional modeling of disease duration in a large cohort of patients (n = 134) and longitudinal analysis in a subset that delayed surgery (n = 31). To track subregional pathology, we applied surface-shape analysis techniques on manual mesiotemporal labels.
Longitudinal and cross-sectional designs showed consistent patterns of progressive atrophy in hippocampal CA1, anterolateral entorhinal, and the amygdalar laterobasal group bilaterally. These regions also exhibited more marked age-related volume loss in patients compared with controls. We found a faster progression of hippocampal atrophy in patients with a seizure frequency ≥6 per month. High rates of contralateral entorhinal cortex atrophy predicted postsurgical seizure relapse.
We observed progressive atrophy in hippocampal, amygdalar, and entorhinal subregions that frequently display neuronal loss on histology. The bilateral character of cumulative atrophy highlights the importance of early surgery. In patients who nevertheless delay this procedure, serial scanning may provide markers of surgical outcome.
... Volumetric analysis demonstrated atrophy in multiple limbic structures, including the hippocampus, entorhinal cortex, amygdala (Cendes et al., 1993a,b;Bernasconi et al., 2001Bernasconi et al., , 2003a, temporopolar, perirhinal, lateral temporal neocortices (Jutila et al., 2001;Moran et al., 2001;Sankar et al., 2008), and the thalamus (Dreifuss et al., 2001;Natsume et al., 2003;Bernhardt et al., 2012). In the hippocampus and thalamus, surface shape mapping has furthermore allowed localizing structural anomalies at a subregional level (Hogan et al., 2004;Kim et al., 2008;Bernhardt et al., 2012, in press). In the thalamus, for example, we found volume loss located primarily in mediodorsal segments (Bernhardt et al., 2012). ...
Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy.
