Isabelle Berry

Early diagnosis of Alzheimer's disease using cortical thickness: impact of cognitive reserve

Brain atrophy measured by magnetic resonance structural imaging has been proposed as a surrogate marker for the early diagnosis of Alzheimers disease. Studies on large samples are still required to determine its practical interest at the individual level, especially with regards to the capacity of anatomical magnetic resonance imaging to disentangle the confounding role of the cognitive reserve in the early diagnosis of Alzheimers disease. One hundred and thirty healthy controls, 122 subjects with mild cognitive impairment of the amnestic type and 130 Alzheimers disease patients were included from the ADNI database and followed up for 24 months. After 24 months, 72 amnestic mild cognitive impairment had converted to Alzheimers disease (referred to as progressive mild cognitive impairment, as opposed to stable mild cognitive impairment). For each subject, cortical thickness was measured on the baseline magnetic resonance imaging volume. The resulting cortical thickness map was parcellated into 22 regions and a normalized thickness index was computed using the subset of regions (right medial temporal, left lateral temporal, right posterior cingulate) that optimally distinguished stable mild cognitive impairment from progressive mild cognitive impairment. We tested the ability of baseline normalized thickness index to predict evolution from amnestic mild cognitive impairment to Alzheimers disease and compared it to the predictive values of the main cognitive scores at baseline. In addition, we studied the relationship between the normalized thickness index, the education level and the timeline of conversion to Alzheimers disease. Normalized thickness index at baseline differed significantly among all the four diagnosis groups (P < 0.001) and correctly distinguished Alzheimers disease patients from healthy controls with an 85% cross-validated accuracy. Normalized thickness index also correctly predicted evolution to Alzheimers disease for 76% of amnestic mild cognitive impairment subjects after cross-validation, thus showing an advantage over cognitive scores (range 63–72%). Moreover, progressive mild cognitive impairment subjects, who converted later than 1 year after baseline, showed a significantly higher education level than those who converted earlier than 1 year after baseline. Using a normalized thickness index-based criterion may help with early diagnosis of Alzheimers disease at the individual level, especially for highly educated subjects, up to 24 months before clinical criteria for Alzheimers disease diagnosis are met.

Integration method of 3D MR spectroscopy into treatment planning system for glioblastoma IMRT dose painting with integrated simultaneous boost

BackgroundTo integrate 3D MR spectroscopy imaging (MRSI) in the treatment planning system (TPS) for glioblastoma dose painting to guide simultaneous integrated boost (SIB) in intensity-modulated radiation therapy (IMRT).MethodsFor sixteen glioblastoma patients, we have simulated three types of dosimetry plans, one conventional plan of 60-Gy in 3D conformational radiotherapy (3D-CRT), one 60-Gy plan in IMRT and one 72-Gy plan in SIB-IMRT. All sixteen MRSI metabolic maps were integrated into TPS, using normalization with color-space conversion and threshold-based segmentation. The fusion between the metabolic maps and the planning CT scans were assessed. Dosimetry comparisons were performed between the different plans of 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy SIB-IMRT, the last plan was targeted on MRSI abnormalities and contrast enhancement (CE).ResultsFusion assessment was performed for 160 transformations. It resulted in maximum differences <1.00 mm for translation parameters and ≤1.15° for rotation. Dosimetry plans of 72-Gy SIB-IMRT and 60-Gy IMRT showed a significantly decreased maximum dose to the brainstem (44.00 and 44.30 vs. 57.01 Gy) and decreased high dose-volumes to normal brain (19 and 20 vs. 23% and 7 and 7 vs. 12%) compared to 60-Gy 3D-CRT (pu2009<u20090.05).ConclusionsDelivering standard doses to conventional target and higher doses to new target volumes characterized by MRSI and CE is now possible and does not increase dose to organs at risk. MRSI and CE abnormalities are now integrated for glioblastoma SIB-IMRT, concomitant with temozolomide, in an ongoing multi-institutional phase-III clinical trial. Our method of MR spectroscopy maps integration to TPS is robust and reliable; integration to neuronavigation systems with this method could also improve glioblastoma resection or guide biopsies.

A multicenter measurement of magnetization transfer ratio in normal white matter

To assess the importance of intercenter variations when measuring magnetization transfer ratio (MTR) in the brain, six European centers measured MTR in normal white matter. MTR ranged from 9 to 51 percent units (25 sequences). The effective flip angle of the saturating pulse divided by the pulse repetition time (ENRsat degrees/msec) was a good predictor of MTR (MTR = 3.25 ENRsat).J. Magn. Reson. Imaging 1999; 9:441–446.

PROTON MAGNETIC RESONANCE SPECTROSCOPIC IMAGING IN NEWLY DIAGNOSED GLIOBLASTOMA : PREDICTIVE VALUE FOR THE SITE OF POSTRADIOTHERAPY RELAPSE IN A PROSPECTIVE LONGITUDINAL STUDY

PURPOSEnTo investigate the association between magnetic resonance spectroscopic imaging (MRSI)-defined, metabolically abnormal tumor regions and subsequent sites of relapse in data from patients treated with radiotherapy (RT) in a prospective clinical trial.nnnMETHODS AND MATERIALSnTwenty-three examinations were performed prospectively for 9 patients with newly diagnosed glioblastoma multiforme studied in a Phase I trial combining Tipifarnib and RT. The patients underwent magnetic resonance imaging (MRI) and MRSI before treatment and every 2 months until relapse. The MRSI data were categorized by the choline (Cho)/N-acetyl-aspartate (NAA) ratio (CNR) as a measure of spectroscopic abnormality. CNRs corresponding to T1 and T2 MRI for 1,207 voxels were evaluated before RT and at recurrence.nnnRESULTSnBefore treatment, areas of CNR2 (CNR > or =2) represented 25% of the contrast-enhancing (T1CE) regions and 10% of abnormal T2 regions outside T1CE (HyperT2). The presence of CNR2 was often an early indicator of the site of relapse after therapy. In fact, 75% of the voxels within the T1CE+CNR2 before therapy continued to exhibit CNR2 at relapse, compared with 22% of the voxels within the T1CE with normal CNR (p < 0.05). The location of new contrast enhancement with CNR2 corresponded in 80% of the initial HyperT2+CNR2 vs. 20.7% of the HyperT2 voxels with normal CNR (p < 0.05).nnnCONCLUSIONnMetabolically active regions represented a small percentage of pretreatment MRI abnormalities and were predictive for the site of post-RT relapse. The incorporation of MRSI data in the definition of RT target volumes for selective boosting may be a promising avenue leading to increased local control of glioblastomas.

Piecemeal recruitment of left-lateralized brain areas during reading: a spatio-functional account.

Neuroimaging studies of reading converge to suggest that linguistically elementary stimuli are confined to the activation of bilateral posterior regions, whereas linguistically complex stimuli additionally recruit left hemispheric anterior regions, raising the hypotheses of a gradual bilateral-to-left and a posterior-to-anterior recruitment of reading related areas. Here, we tested these two hypotheses by contrasting a repertoire of eight categories of stimuli ranging from simple orthographic-like characters to words and pseudowords in a single experiment, and by measuring BOLD signal changes and connectivity while 16 fluent readers passively viewed the stimuli. Our results confirm the existence of a bilateral-to-left and posterior-to-anterior recruitment of reading related areas, straightforwardly resulting from the increase in stimulis linguistic processing load, which reflects reading processes: visual analysis, orthographic encoding and phonological decoding. Connectivity analyses strengthened the validity of these observations and additionally revealed an enhancement of the left parieto-frontal information trafficking for higher linguistic processing. Our findings clearly establish the notion of a gradual spatio-functional recruitment of reading areas and demonstrate, to the best of our knowledge, the first evidence of a robust and staged link between the level of linguistic processing, the spatial distribution of brain activity and its information trafficking.

Quantitative and reproducibility study of four tractography algorithms used in clinical routine.

To evaluate fiber tracking strategy in terms of acquisition schemes in conjunction with four algorithms used in clinical routine, we studied one of the major tracts, anatomically well known, and which should be preserved as much as possible during neurosurgery: the corticospinal tract.

New concept of myocardial longitudinal strain reserve assessed by a dipyridamole infusion using 2D-strain echocardiography: the impact of diabetes and age, and the prognostic value.

AimsAlthough dipyridamole is a widely used pharmacological stress agent, the direct effects on myocardium are not entirely known. Diabetic cardiomyopathy can be investigated by 2D-strain echocardiography. The aim of this study was to assess myocardial functional reserve after dipyridamole infusion using speckle-tracking echocardiography.MethodsSeventy-five patients referred for dipyridamole stress myocardial perfusion gated SPECT (MPGS) were examined by echocardiography to assess a new concept of longitudinal strain reserve (LSR) and longitudinal strain rate reserve (LSRR) respectively defined by the differences of global longitudinal strain (GLS) and longitudinal strain rate between peak stress after dipyridamole and rest. Twelve patients with myocardial ischemia were excluded on the basis of MPGS as gold standard.ResultsMean LSR was −2.28±2.19% and was more important in the 28 (44%) diabetic patients (−3.27±1.93%; p = 0.001). After multivariate analyses, only diabetes improved LSR (p = 0.011) after dipyridamole infusion and was not associated with glycaemic control (p = 0.21), insulin therapy (p = 0.46) or duration of the disease (p = 0.80). Conversely, age (p = 0.002) remained associated with a decrease in LSR. LSSR was also correlated to age (p = 0.005). Patients with a LSR < 0% have a better survival after 15 months (log-rank p = 0.0012).ConclusionLSR explored by 2D speckle-tracking echocardiography after dipyridamole infusion is a simple and new concept that provides new insights into the impact of diabetes and age on the myocardium with a potential prognostic value.

Evaluation of the Lactate-to-N-Acetyl-aspartate Ratio Defined With Magnetic Resonance Spectroscopic Imaging Before Radiation Therapy as a New Predictive Marker of the Site of Relapse in Patients With Glioblastoma Multiforme

PURPOSEnBecause lactate accumulation is considered a surrogate for hypoxia and tumor radiation resistance, we studied the spatial distribution of the lactate-to-N-acetyl-aspartate ratio (LNR) before radiation therapy (RT) with 3D proton magnetic resonance spectroscopic imaging (3D-(1)H-MRSI) and assessed its impact on local tumor control in glioblastoma (GBM).nnnMETHODS AND MATERIALSnFourteen patients with newly diagnosed GBM included in a phase 2 chemoradiation therapy trial constituted our database. Magnetic resonance imaging (MRI) and MRSI data before RT were evaluated and correlated to MRI data at relapse. The optimal threshold for tumor-associated LNR was determined with receiver-operating-characteristic (ROC) curve analysis of the pre-RT LNR values and MRI characteristics of the tumor. This threshold was used to segment pre-RT normalized LNR maps. Two spatial analyses were performed: (1) a pre-RT volumetric comparison of abnormal LNR areas with regions of MRI-defined lesions and a choline (Cho)-to- N-acetyl-aspartate (NAA) ratio ≥ 2 (CNR2); and (2) a voxel-by-voxel spatial analysis of 4,186,185 voxels with the intention of evaluating whether pre-RT abnormal LNR areas were predictive of the site of local recurrence.nnnRESULTSnA LNR of ≥ 0.4 (LNR-0.4) discriminated between tumor-associated and normal LNR values with 88.8% sensitivity and 97.6% specificity. LNR-0.4 voxels were spatially different from those of MRI-defined lesions, representing 44% of contrast enhancement, 64% of central necrosis, and 26% of fluid-attenuated inversion recovery (FLAIR) abnormality volumes before RT. They extended beyond the overlap with CNR2 for most patients (median: 20 cm(3); range: 6-49 cm(3)). LNR-0.4 voxels were significantly predictive of local recurrence, regarded as contrast enhancement at relapse: 71% of voxels with a LNR-0.4 before RT were contrast enhanced at relapse versus 10% of voxels with a normal LNR (P<.01).nnnCONCLUSIONSnPre-RT LNR-0.4 in GBM indicates tumor areas that are likely to relapse. Further investigations are needed to confirm lactate imaging as a tool to define additional biological target volumes for dose painting.

Can DTI fiber tracking of the optic radiations predict visual deficit after surgery

OBJECTnSparing optic radiations can be of paramount importance during epilepsy surgery of the temporal lobe. The anatomical heterogeneity of the Meyers loop of the optic radiations could be assessed by means of diffusion tensor tractography. We used temporal lobe surgery as a lesion model to validate this method.nnnMATERIAL AND METHODSnWe analyzed the distance between the temporal pole (TP) and Meyers loop (ML) and the correlation between visual impairment and the percentage of virtual fibers injured. MRI studies were performed in 18 patients and 13 controls. Diffusion tensor imaging (DTI) with fiber tracking was performed using four different algorithms and various gradient directions (15 or 32) and fractional anisotropy (FA) thresholds (0.18, 0.20, and 0.22). To find the best DTI model, we tested each gradient direction and FA threshold on 16 operated patients by pre- and post-operative visual field testing that analyzed the percentage of virtual fibers damaged on 3-month-post-operative MRIs.nnnRESULTSnMarked individual differences were noted in the TP-ML distances (mean: 25.4mm; range 18.2-38.3mm; standard deviation: 4.7) but with no significant difference between patients and controls (p=0.9). The percentage of virtual fibers reconstructed by tracking and damaged by surgery was correlated with visual impairment. Significant differences appeared between algorithm types. The tensor-line algorithm with 15-direction resolution and an anisotropy threshold of 0.18 seemed to be the most relevant. A threshold of 5.5% of injured virtual fiber could predict a visual defect with a sensitivity of 71.4% and a specificity of 87.5%.nnnCONCLUSIONnOptic radiation tractography by DTI could be a useful method to assess an individual patients risk of postoperative visual deficit.

Pilot study for left ventricular imaging phenotype of patients over 65 years old with heart failure and preserved ejection fraction: the high prevalence of amyloid cardiomyopathy.

This study sought to phenotype patients over 65xa0years old with heart failure and preserved ejection fraction (HFpEF) using clinical available comprehensive cardiovascular imaging modalities. Forty-nine patients with HFpEF and without coronary artery disease underwent clinical evaluation, electrocardiography, echocardiography, cardiac magnetic resonance (CMR) and 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy (99mTc-DPD). The mean population age was 76u2009±u20098 years. Most of the patients (53u2009%) were NYHA class II. Mean NT-Pro-NBNP level was 1961u2009±u20092372xa0pg/ml. CMR exhibited a hypertrophic cardiomyopathy or infiltrative pattern in 3 (6u2009%) and 15 (31u2009%) patients, respectively. In the latter subgroup, 99mTc-DPD was suggestive of transthyretin-related cardiac amyloidosis for nine (18u2009%) patients, while AL amyloidosis was proven in five patients (10u2009%) by extracardiac (nu2009=u20093, 6u2009%) or endomyocardial (nu2009=u20092, 4u2009%) biopsies—one patient declined tissue biopsy. Compared to patients with unspecified cardiomyopathy (nu2009=u200931), patients with amyloid cardiomyopathy (nu2009=u200915 or nu2009=u200914/proven) had less hypertension, lower systolic blood pressure and higher NT-pro BNP level. Their electrocardiogram showed lowest QRS voltage and longer QRS duration. Left ventricular (LV) pattern was characterized by a more pronounced LV hypertrophy, a smaller ejection fraction and a decrease of global longitudinal strain associated with an increase of longitudinal strain apical-to-basal ratio. In patients over 65xa0years, HFpEF is a heterogeneous syndrome with at least a 29u2009% prevalence of amyloid cardiomyopathy. Combined CMR and 99mTc-DPD are helpful imaging tools for accurate phenotyping of patients amenable to histopathological diagnosis or genetic testing, and should be considered for proper management of this population. Further longitudinal investigations are needed to better clarify these preliminary results.