Search

OBJECTIVE In patients with temporal lobe epilepsy (TLE) with a nonlesional and nonepileptogenic hippocampus (HC), in order to preserve functionally intact brain tissue, the HC is not resected. However, some patients experience postoperative memory decline, possibly due to disruption of the extrahippocampal memory network and secondary hippocampal volume (HV) loss. The purpose of this study was to determine the extent of hippocampal atrophy ipsilateral and contralateral to the side of the surgery and its relation to memory outcomes. METHODS Hippocampal volume and verbal as well as visual memory performance were retrospectively examined in 55 patients (mean age ± standard deviation [SD] 30 ± 15 years, 25 female, 31 left) before and 5 months after surgery within the temporal lobe that spared the entire HC. HV was extracted based on prespecified templates, and resection volumes were also determined. RESULTS HV loss was found both ipsilateral and contralateral to the side of surgery (P

BACKGROUND Hemodynamic alterations of extracranial veins are considered an etiologic factor in multiple sclerosis (MS). However, ultrasound and MRI studies could not confirm a pathophysiological link. Because of technical challenges using standard diagnostics, information about the involvement of superficial intracranial veins in proximity to the affected brain in MS is scarce. PURPOSE To comprehensively investigate the hemodynamics of intracranial veins and of the venous outflow tract in MS patients and controls. STUDY TYPE Prospective. POPULATION Twenty-eight patients with relapsing-remitting MS (EDSS1.9 ± 1.1; range 0-3) and 41 healthy controls. FIELD STRENGTH/SEQUENCE 3T/2D phase-contrast and time-resolved 4D flow MRI, extra- and transcranial sonography. ASSESSMENT Hemodynamics within the superficial and deep intracranial venous system and outflow tract including the internal, basal, and great cerebral vein, straight, superior sagittal, and transverse sinuses, internal jugular and vertebral veins. Sonography adhered to the chronic cerebrospinal venous insufficiency (CCSVI) criteria. STATISTICAL TESTS Multivariate repeated measure analysis of variance, Student's two-sample t-test, chi-square, Fisher's exact test; separate analysis of the entire cohort and 32 age- and sex-matched participants. RESULTS Multi- and univariate main effects of the factor group (MS patient vs. control) and its interactions with the factor vessel position (lower flow within dorsal superior sagittal sinus in MS, 3 ± 1 ml/s vs. 3.8 ± 1 ml/s; P < 0.05) in the uncontrolled cohort were attributable to age-related differences. Age- and sex-matched pairs showed a different velocity gradient in a single segment within the deep cerebral veins (great cerebral vein, vena cerebri magna [VCM] 7.6 ± 1.7 cm/s; straight sinus [StS] 10.5 ± 2.2 cm/s vs. volunteers: VCM 9.2 ± 2.3 cm/s; StS 10.2 ± 2.3 cm/s; P = 0.01), reaching comparable velocities instantaneously downstream. Sonography was not statistically different between groups. DATA CONCLUSION Consistent with previous studies focusing on extracranial hemodynamics, our comprehensive analysis of intracerebral venous blood flow did not reveal relevant differences between MS patients and controls. Level of Evidence 1. Technical Efficacy Stage 3. J. Magn. Reson. Imaging 2020;51:205-217.

PURPOSE Achieving higher spatial resolution and improved brain coverage while mitigating in-plane susceptibility artifacts in the assessment of perfusion parameters, such as cerebral blood volume, in echo planar imaging (EPI)-based dynamic susceptibility contrast weighted cerebral perfusion measurements. METHODS PEAK-EPI, an EPI sequence with interleaved readout trajectories and three different strategies for autocalibration-signal acquisition (inplace, dynamic extra and extra) is presented. Performance of each approach is analyzed in vivo based on flip angle variation induced dynamics, assessing temporal fidelity, temporal SNR and g-factors. All approaches are compared with conventional GRAPPA reconstructions. PEAK-EPI with inplace autocalibration-signal at R = 5 is then compared with the standard clinical EPI protocol in six patients, using two half-dose dynamic susceptibility contrast weighted cerebral perfusion measurements per subject. RESULTS PEAK-EPI acquisition facilitates a substantial increase of spatial resolution at a higher number of slices per TR and provides improved SNR compared to conventional GRAPPA. High dependency of the resulting reconstruction quality on the type of autocalibration-signal acquisition is observed. PEAK-EPI with inplace autocalibration-signal achieves high temporal fidelity and initial feasibility is shown. CONCLUSION The obtained high resolution cerebral blood volume maps reveal more detailed information than in corresponding standard EPI measurements and facilitate detailed delineation of tumorous tissue. Magn Reson Med 77:2153-2166, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Objective Spatial neglect can either spontaneously resolve or persist after stroke; the latter is associated with a poorer outcome. We aimed to investigate the neural correlates and predictors of favorable versus poor recovery from neglect in acute stroke. Methods In addition to neuropsychological testing, we explored task-related functional magnetic resonance imaging activation and functional connectivity in 34 patients with neglect and/or extinction. Patients were examined at 2 to 3 days (acute phase I) and 8 to 10 days (acute phase II), and some of them at 4 to 6 months (chronic phase) poststroke. Results Course of recovery was predicted by the strength of functional connectivity between the right parietal and left prefrontal and parietal regions, as early as acute phase I. During acute phase II, favorable recovery from neglect was associated with increased activation in the left prefrontal and right parietal regions, an effect not observed at any time point in patients with poor acute recovery. The extent of neglect amelioration correlated with activation gain in the right attention centers; stronger activation of their left functional homologues correlated with better spatial processing in the neglected hemispace during both of the acute examination phases. Interpretation System excitability and early recruitment of contralesional functional homologues represented specific features of favorable recovery in acute stroke. In severe strokes leading to neglect, contralesional functional homologues support recovery by modulating the preserved ipsilesional network, and initial functional connectivity between them might predict recovery course and help to identify patients with potentially poor recovery requiring more intensive early rehabilitation.

Purpose To compare the vessel size and the cerebral blood volume in human gliomas with histopathology. Vessel size imaging (VSI) is a dynamic susceptibility contrast method for the assessment of the vessel size in normal and pathological tissue. Previous publications in rodents showed a satisfactory conformity with the vessel size derived from histopathology. To assess the clinical value, further, the progression-free interval was determined and correlated. Materials and Methods Twenty-five gliomas (WHO grade °II [n = 10], °III [n = 3], °IV [n = 12]) were prospectively included and received a stereotaxic biopsy after VSI. The vessel size and the cerebral blood volume (CBV) were calculated in regions of interest at the tumor edge and correlated with the vessel size measured by histopathology. Results Both VSI and CBV showed a good correlation with the vessel size in histopathology (up to r = 0.84, P < 0.001, and r = 0.62, P < 0.001, respectively). Slope and offset of the linear regression (y = 0.77x + 0.36 μm) suggest that the size of normal capillaries is overestimated with VSI, while for grossly enlarged vessels an underestimation occurs. Both VSI and CBV were negatively correlated with the progression-free interval (r = –0.57, P = 0.008, and r = –0.50, P = 0.025, respectively). Conclusion The correlation between VSI and vessel size from histopathology is in good accordance with the animal studies. The overestimation of small capillary sizes is also known from the animal trials. Vessel size and CBV showed similar results, both for the correlation with the histopathological vessel size and the progression-free interval. J. Magn. Reson. Imaging 2015;42:1117–1125.

Microelectrocorticography (µECoG) provides insights into the cortical organization with high temporal and spatial resolution desirable for better understanding of neural information processing. Here we evaluated the use of µECoG for detailed cortical recording of somatosensory evoked potentials (SEPs) in an ovine model. The approach to the cortex was planned using an MRI-based 3D model of the sheep's brain. We describe a minimally extended surgical procedure allowing placement of two different µECoG grids on the somatosensory cortex. With this small craniotomy, the frontal sinus was kept intact, thus keeping the surgical site sterile and making this approach suitable for chronic implantations. We evaluated the procedure for chronic implantation of an encapsulated µECoG recording system. During acute and chronic recordings, significant SEP responses in the triangle between the ansate, diagonal, and coronal sulcus were identified in all animals. Stimulation of the nose, upper lip, lower lip, and chin caused a somatotopic lateral-to-medial, ipsilateral response pattern. With repetitive recordings of SEPs, this somatotopic pattern was reliably recorded for up to 16 weeks. The findings of this study confirm the previously postulated ipsilateral, somatotopic organization of the sheep's sensory cortex. High gamma band activity was spatially most specific in the comparison of different frequency components of the somatosensory evoked response. This study provides a basis for further acute and chronic investigations of the sheep's sensory cortex by characterizing its exact position, its functional properties, and the surgical approach with respect to macroanatomical landmarks.

Visual neglect results from dysfunction within the spatial attention network. The structural connectivity in undamaged brain tissue in neglect has barely been investigated until now. In the present study, we explored the microstructural white matter characteristics of the contralesional hemisphere in relation to neglect severity and recovery in acute stroke patients. We compared age-matched healthy subjects and three groups of acute stroke patients (9 ± 0.5 days after stroke): (i) patients with nonrecovered neglect (n = 12); (ii) patients with rapid recovery from initial neglect (within the first week post-stroke, n = 7), (iii) stroke patients without neglect (n = 17). We analyzed the differences between groups in grey and white matter density and fractional anisotropy (FA) and used fiber tracking to identify the affected fibers. Patients with nonrecovered neglect differed from those with rapid recovery by FA-reduction in the left inferior parietal lobe. Fibers passing through this region connect the left-hemispheric analogues of the ventral attention system. Compared with healthy subjects, neglect patients with persisting neglect had FA-reduction in the left superior parietal lobe, optic radiation, and left corpus callosum/cingulum. Fibers passing through these regions connect centers of the left dorsal attention system. FA-reduction in the identified regions correlated with neglect severity. The study shows for the first time white matter changes within the spatial attention system remote from the lesion and correlating with the extent and persistence of neglect. The data support the concept of neglect as disintegration within the whole attention system and illustrate the dynamics of structural-functional correlates in acute stroke. Hum Brain Mapp 35:4678–4692, 2014. © 2014 Wiley Periodicals, Inc.

Purpose We recently presented a method for the quantitative measurement of the arterial input function which allows for determination of absolute cerebral blood flow (CBF) values without adjustable parameters. The aim of the present work is to estimate absolute CBF values by using this new technique and to compare it with the gold standard for cerebral perfusion, positron emission tomography. Methods Pigs (13) were comparatively investigated by each method performing multiple measurement runs. The reproducibility of both methods was assessed by a voxel-wise correlation of repeated measurements. An intersubject evaluation was performed on median whole-brain CBF estimates. Results The mean CBF (MRI) was for gray matter, the mean CBF (positron emission tomography) was for gray and white matter. The reproducibility for MRI correlated with r = 0.85 and , for positron emission tomography with r = 0.76 and . The correlation for the median whole-brain CBF in MRI and positron emission tomography was r = 0.60 and P = 0.04. Conclusions The proposed method allows for determination of quantitative CBF without normalization factors. The relatively low estimates of absolute CBF most likely results from the higher age of the pigs as compared to other studies. The intermediate correlation between both methods is caused by physiological intraindividual fluctuations of the CBF and by a limited reproducibility of both methods. Magn Reson Med 72:1723–1734, 2014. © 2013 Wiley Periodicals, Inc.

Imaging of cerebral perfusion by tracking the first passage of an exogenous paramagnetic contrast agent (termed dynamic susceptibility contrast, MRI) has been used in the clinical practice for about a decade. However, the primary goal of dynamic susceptibility contrast MRI to directly quantify the local cerebral blood flow remains elusive. The major challenge of dynamic susceptibility contrast MRI is to measure the contrast inflow to the brain, i.e., the arterial input function. The measurement is complicated by the limited dynamic range of MRI pulse sequences that are optimized for a good contrast in brain tissue but are suboptimal for a much higher tracer concentration in arterial blood. In this work, we suggest a novel method for direct arterial input function quantification. The arterial input function is measured in the carotid arteries with a dedicated plug-in to the conventional pulse sequence to enable resolution of T(2) on the order of a millisecond. The new technique is compatible with the clinical measurement protocols. Applied to the pig model (N = 13), the method demonstrates robustness of the arterial input function measurement. The cardiac output and cerebral blood volume, obtained without adjustable parameters, agree well with positron emission tomography measurements and values found in the literature.

A novel method of automated MRI volumetry was used to study regional atrophy and disease progression in repeated MRI measurements of patients with frontotemporal lobar degeneration (FTLD). Fifty‐nine structural MRI data sets of 17 clinically diagnosed FTLD patients were acquired over up to 30 months in intervals of 6 months and compared with data of 30 age‐matched healthy controls. Patients were further subgrouped into behavioral variant FTLD (bvFTLD), progressive nonfluent aphasia (PNFA), and semantic dementia (SemD). Gray matter (GM) volumes of frontal lobes (FL) and temporal lobes (TL) were determined by voxel‐based volumetry based on SPM5 algorithms and a probabilistic brain atlas. MRI volumetry revealed frontal and temporal GM atrophy across FTLD patients, with further progression over time. Significant side asymmetry of TL volumes was found in SemD. The ratio of TL to FL volumes was significantly reduced in SemD and increased in bvFTLD. Using this ratio, 6/7 SemD patients and 5/6 bvFTLD patients could be correctly differentiated. TL/FL ratios in bvFTLD and SemD further diverged significantly over a time span of only 6 months. Rates of temporal GM loss per 6 months were 3–4% in SemD, and 2.5% for frontal GM loss in bvFTLD, and thereby clearly exceeded published cerebral volume loss in healthy elderly subjects. The study presents a fully automated, observer‐independent volumetric assessment of regional atrophy which allows differentiation of FTLD subgroups. Its sensitivity for atrophy progression—even in such short intervals like 6 months—might benefit future clinical trials as treatment outcome measure. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.

Reconstruction of neuronal fibers using diffusion-weighted (DW) MRI is an emerging method in biomedical research. Existing fiber-tracking algorithms are commonly based on the “walker principle.” Fibers are reconstructed as trajectories of “walkers,” which are guided according to local diffusion properties. In this study, a new method of fiber tracking is proposed that does not engage any “walking” algorithm. It resolves a number of inherent problems of the “walking” approach, in particular the reconstruction of crossing and spreading fibers. In the proposed method, the fibers are built with small line elements. Each line element contributes an anisotropic term to the simulated DW signal, which is adjusted to the measured signal. This method demonstrates good results for simulated fibers. A single in vivo result demonstrates the successful reconstruction of the dominant neuronal pathways. A comparison with the diffusion tensor imaging (DTI)-based fiber assignment with continuous tracking (FACT) method and the probabilistic index of connectivity (PICo) method based on a multitensor model is performed for the callosal fibers. The result shows a strong increase in the number of reconstructed fibers. These almost fill the total white matter (WM) volume and connect a large area of the cortex. The method is very computationally expensive. Possible ways to address this problem are discussed. Magn Reson Med 60:953–963, 2008. © 2008 Wiley-Liss, Inc.

Progressive multifocal leukoencephalopathy (PML) is caused by the replication of JC virus in oligodendrocytes of immunocompromised patients. Diagnosis usually relies on the polymerase chain reaction (PCR)-based demonstration of JC virus DNA in the cerebrospinal fluid. As previous reports have suggested that some patients may benefit from antiviral therapy, non-invasive early diagnosis is highly desirable. Repetitive magnetic resonance imaging (MRI) examinations (two to nine) were obtained in seven patients (aged 40-67 years, six males, one female) with classical clinical and imaging findings of PML. Five patients had underlying hematological disorders and two acquired immune deficiency syndrome. PCR of the cerebrospinal fluid (CSF) specimen was positive for JC virus DNA in six patients. MRI sequences included T2-, T1- and diffusion-weighted (DW) images in all patients and diffusion-tensor imaging (DTI) in four cases. DTI was once performed at 3T, in the remaining patients at 1.5T. All patients received antiviral treatment with cidofovir in addition to the treatment of the underlying disorder. MRI showed areas of T2 hyperintensity with involvement of the subcortical U-fibers and restricted diffusion in all patients. Areas of diffusion abnormality correlated with disease progress. Contrast enhancement was encountered once after successful treatment and heralded clinical remission with virus elimination from the CSF. Hence, MRI including DW and contrast-enhanced images may be used to evaluate disease activity. Contrast enhancement may indicate an inflammatory response and thus herald immunologic virus elimination.

A multidiffusion-tensor model (MDT) is presented containing two anisotropic and one isotropic diffusion tensors. This approach has the ability to detect areas of fiber crossings and resolve the direction of crossing fibers. The mean diffusivity and the ratio of the tensor compartments were merged to one independent parameter by fitting MDT to the diffusion-weighted intensities of a two-point data acquisition scheme. By an F-test between the errors of the standard single diffusion tensor and the more complex MDT, fiber crossings were detected and the more accurate model was chosen voxel by voxel. The performance of crossing detection was compared with the spherical harmonics approach in simulations as well as in vivo. Similar results were found in both methods. The MDT model, however, did not only detect crossings but also yielded the single fiber directions. The FACT algorithm and a probabilistic connectivity algorithm were extended to support the MDT model. For example, a mean angular error smaller than 10 degrees was found for the MDT model in a simulated fiber crossing with an SNR of 80. By tracking the corticospinal tract the MDT-based tracks reached a significantly greater area of the gyrus precentralis.

Positron emission tomography (PET) using [11C]PK 11195, a ligand for peripheral benzodiazepine receptor binding sites, offers the opportunity to image activated microglia in vivo. This tool may therefore be used to display the occurrence of microglial activation in the course of neurodegeneration. A patient with the clinical diagnosis of corticobasal degeneration (CBD) and left-sided symptoms was studied using fluorodeoxyglucose (FDG) and [11C]PK 11195 PET. We found a marked right hemispheric hypometabolism and asymmetric microglial activation in corresponding areas of the basal ganglia and right temporal and parietal cortex. [11C]PK 11195 PET suggests involvement of microglial activation in the pathogenesis of CBD. © 2004 Movement Disorder Society

In vivo longitudinal relaxation times of N-acetyl compounds (NA), choline-containing substances (Cho), creatine (Cr), myo-inositol (mI), and tissue water were measured at 1.5 and 3 T using a point-resolved spectroscopy (PRESS) sequence with short echo time (TE). T(1) values were determined in six different brain regions: the occipital gray matter (GM), occipital white matter (WM), motor cortex, frontoparietal WM, thalamus, and cerebellum. The T(1) relaxation times of water protons were 26-38% longer at 3 T than at 1.5 T. Significantly longer metabolite T(1) values at 3 T (11-36%) were found for NA, Cho, and Cr in the motor cortex, frontoparietal WM, and thalamus. The amounts of GM, WM, and cerebrospinal fluid (CSF) within the voxel were determined by segmentation of a 3D image data set. No influence of tissue composition on metabolite T(1) values was found, while the longitudinal relaxation times of water protons were strongly correlated with the relative GM content.

Short echo time (TE) proton MR spectra of the brain include signals of several metabolites as well as macromolecules. In various pathologies, such as brain tumors and multiple sclerosis (MS), the presence of mobile lipids or pathologically altered macromolecules may provide useful additional diagnostic information. A reliable quantitation of these resonances, however, is often not possible due to the lack of adequate prior knowledge. Furthermore, even if advanced fitting procedures are used, a reliable evaluation of metabolites in the presence of pathological lipids or macromolecules often fails if the latter are omitted in the spectral evaluation. In this study, a method is presented for the simultaneous evaluation of all visible components, including metabolites, lipids, and macromolecules, by the use of the fitting procedure LCModel. A standard basis set of brain metabolites was extended by inclusion of parameterized components for macromolecules and lipids that were derived from metabolite-nulled in vivo spectra of normal brain and high-grade gliomas, respectively. The improved spectral quantitation is demonstrated in glial brain tumors and MS lesions as well as in normal brain. It is pointed out that both macromolecules and lipids must be included to provide a proper spectral evaluation.

Purpose To investigate whether glutamine and glutamate (Glx) were elevated in Kennedy Disease (KD), and whether pathological proteins were spectroscopically visible as altered macromolecular (MM) resonances. Materials and Methods Ten patients with KD and twelve healthy volunteers were investigated using a stimulated echo acquisition mode (STEAM) spectroscopy sequence with metabolite-nulling. Results The concentrations of Glx remained unchanged in KD. An increased myo-inositol (Ins), and elevated MM at 0.9 ppm were found within the motor area. The N-acetyl-aspartate (NAA)/creatine (Cr) ratio was negatively correlated to the number of cytosine adenosine guanine (CAG) repeats in the motor area. Conclusion The elevated MM at 0.9 ppm may be attributed to a pathologically altered protein in KD. Additionally, the changes of Ins point to a clinically unexpected involvement of the motor cortex. The correlation of NAA/Cr with the number of CAG repeats indicates a link between metabolites and genetic failure. J. Magn. Reson. Imaging 2002;16:160–167. © 2002 Wiley-Liss, Inc.

In short echo time proton MR spectra of the brain, resonances from macromolecules are visible. The macromolecular resonances in the 0.5-2.0 ppm region can be affected by lipid contamination arising from fat-containing regions outside the selected volume of interest (VOI). This study demonstrates that considerable lipid contamination may remain in stimulated echo acquisition mode (STEAM) spectra even if the spoiling of unwanted coherences is sufficient and the VOI is placed 2 cm or more away from fat-containing regions. The observed contamination was attributed to residual remote out-of-volume excitation, although only very small out-of-slice ripples of less than 0.2% of the in-slice excitation were found in the calculated excitation profile of the RF pulses. Spatial presaturation of fat-containing regions led to a sufficient suppression of the contamination and enabled the detection of highly reproducible macromolecular resonances. Thus, in single-volume spectroscopy as well as in spectroscopic imaging (SI or CSI), the combination of volume selection and outer volume presaturation, each in three dimensions, is highly recommended to ensure accurate detection and reliable evaluation of even small pathological alterations in macromolecules, e.g., proteins or lipids, or other resonances in the 0.5-2.0 ppm region.

ECGs, vital sign measurements, and laboratory parameters. PK parameters were derived from plasma concentrations versus time data in young and elderly female subjects. Results: Among 304 enrolled subjects, 60 were randomized and treated with BMS-241027 (n1⁄445) or placebo (n1⁄415). There were no deaths or discontinuations due to AEs and most AEs were mild. One patient experienced a Grade 3 hypersensitivity reaction w2.5 hours after the fourth and final dose of 0.002 mg/kg BMS-241027 (5-minute IV infusion), that responded to treatment without residual symptoms. Infusion time was lengthened to 60 minutes for remaining dose panels without additional hypersensitivity reactions. Overall, AEs occurred in 44 (73.3%) subjects: BMS-241027, 35 (77.8%); placebo, 9 (60%). The most common AEs were constipation (33.3%) and headache (30%) without cognitive or peripheral nervous system AEs. No clinically significant abnormalities were observed in ECG parameters, vital signs, or laboratory parameters. BMS-241027 exposure (Cmax and AUC) increased dose proportionately with negligible accumulation after once-weekly administration, without evidence of time-dependent PK.Elderly subjects at 0.02 mg/kg had 2-6 fold higher exposures than young subjects. Conclusions: BMS-241027 was well-tolerated at multiple once-weekly doses up to 0.06 mg/kg, and single doses up to 0.2 mg/kg; the MTD was not achieved. Overall, healthy female subjects given lower doses with prolonged infusion times showed better safety than subjects dosed in oncology trials. These data support future investigation of BMS-241027 in the treatment of AD and other tauopathies.

Several multi-dimensional statistical evaluation methods were applied to single-voxel proton MR spectra of glial brain tumors and of healthy volunteers. Metabolic coordinates with histological relevance for future diagnosis were found by which spectra from controls, low-grade tumors, and high-grade tumors were completely separated. Significant differences between low-grade and high-grade glioma patients and controls were found for several metabolic ratios by variance analysis. Cluster analysis both with and without principal component analysis was applied. The outcome of these two approaches depended mainly on the lipid-to-creatine ratio. Two other approaches, discriminant factor analysis and the orthonormal discriminant vector method were then used to find discriminatory metabolic coordinates. It turned out that a linear combination of all evaluable metabolic ratios made it possible to separate the three groups completely. On the basis of these results, a classification method that uses the entire proton MRS spectrum is proposed.

Brain 2003 for details), setting the significance level at p (uncorrected) < 0.005. To assess subregional hippocampal atrophy, the resulting GM SPM-Tmaps were then superimposed onto the 3D representation of the hippocampi using the Anatomist/BrainVISA software, as already used (Ch etelat et al., Neuropsychologia 2008) and validated (La Joie et al., NeuroImage 2010) elsewhere.Results:Episodic encoding impairment specifically correlated with CA1 subfield GM atrophy (Figure 1B), in reference to hippocampal MRI atlas obtained frommanual delineation (La Joie et al., NeuroImage 2010 Figure 1A), but not with WM atrophy. In contrast, the weak correlation of retrieval scores with hippocampal GM did not point to a particular subfield (Figure 1C), while it was strong with WM, especially in medial parietal and frontal areas (Figure 1D). Conclusions: In aMCI patients, encoding impairment appears specifically related to GM atrophy of the CA1 hippocampal subfield, consistently with the predominant encoding deficits and predominant CA1 atrophy inMCI. In contrast, episodic retrieval deficits seem to be underlain by more distributed tissue losses, consistent with a disruption of a hippocampo-parieto-frontal network. Overall, the specific involvement of the CA1 hippocampal subfield atrophy in episodic encoding deficits in aMCI patients emphasizes this particular subfield as a potential future therapeutic target.