Geon-Ho Jahng

Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease

Background: Neuroimaging in mild cognitive impairment (MCI) and Alzheimer disease (AD) generally shows medial temporal lobe atrophy and diminished glucose metabolism and cerebral blood flow in the posterior cingulate gyrus. However, it is unclear whether these abnormalities also impact the cingulum fibers, which connect the medial temporal lobe and the posterior cingulate regions. Objective: To use diffusion tensor imaging (DTI), by measuring fractional anisotropy (FA), to test 1) if MCI and AD are associated with DTI abnormalities in the parahippocampal and posterior cingulate regions of the cingulum fibers; 2) if white matter abnormalities extend to the neocortical fiber connections in the corpus callosum (CC); 3) if DTI improves accuracy to separate AD and MCI from healthy aging vs structural MRI. Methods: DTI and structural MRI were preformed on 17 patients with AD, 17 with MCI, and 18 cognitively normal (CN) subjects. Results: FA of the cingulum fibers was significantly reduced in MCI, and even more in AD. FA was also significantly reduced in the splenium of the CC in AD, but not in MCI. Adding DTI to hippocampal volume significantly improved the accuracy to separate MCI and AD from CN. Conclusion: Assessment of the cingulum fibers using diffusion tensor imaging may aid early diagnosis of Alzheimer disease.

Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI.

Objectives: To test if arterial spin labeling (ASL) MRI could detect a pattern of hypoperfusion in frontotemporal dementia (FTD) vs cognitively normal (CN) control subjects; to determine the regional difference of perfusion between FTD and Alzheimer disease (AD); and to determine whether hypoperfusion in FTD correlates with cognitive impairment. Methods: We included 21 patients with FTD, 24 patients with AD, and 25 CN subjects in this cross-sectional MRI study. All subjects had MRI scans including T1-weighted structural images and ASL-MR images. Results: ASL-MRI detected a pattern of hypoperfusion in right frontal regions in patients with FTD vs CN subjects, similar to PET and SPECT. FTD had higher perfusion than AD in the parietal regions and posterior cingulate. Frontal hypoperfusion in FTD correlated with deficits in judgment and problem solving. Adding frontal perfusion to gray matter (GM) atrophy significantly improved the classification of FTD from normal aging to 74%, and adding parietal perfusion to GM atrophy significantly improved the classification of FTD from AD to 75%. Combining frontal and parietal lobe perfusion further improved the classification of FTD from AD to 87%. Conclusion: Frontotemporal dementia and Alzheimer disease display different spatial distributions of hypoperfusion on arterial spin labeling MRI. With further development and evaluation, arterial spin labeling MRI could contribute to the differential diagnosis between frontotemporal dementia and Alzheimer disease.

Pediatric Perfusion Imaging Using Pulsed Arterial Spin Labeling

To test the feasibility of pediatric perfusion imaging using a pulsed arterial spin labeling (ASL) technique at 1.5 T.

High resolution wall and lumen MRI of the middle cerebral arteries at 3 tesla.

Background: Although black-blood MRI (BB-MRI) can identify plaques in the cervical carotid arteries, this modality has not been applied in intracranial arteries. We imaged the lumina and walls of stenotic middle cerebral arteries (MCAs) in symptomatic and asymptomatic patients using high-resolution BB-MRI, in order to characterize vulnerable plaques and to determine the diagnostic accuracy of BB-MRI in MCA stenosis. Methods: Multicontrast (T1, T2 and proton density)-weighted BB-MRIs were acquired in 15 patients with MCA stenosis and in 2 volunteers. Each MCA was classified into one of three groups based on MR angiographic findings and symptoms: normal, symptomatic stenosis, or asymptomatic stenosis. The plaque signal intensity was interpreted and the total wall thickness was measured at the most stenotic segment. These values were then compared between asymptomatic and symptomatic MCAs using t test. For assessment of lumen imaging, the MCA stenosis graded on BB-MR images was compared with that graded on conventional angiography (digital subtraction angiography). Results: Twenty-eight MCAs were evaluated (normal MCAs: 12, symptomatic stenoses: 7, and asymptomatic stenoses: 9). T1- and/or T2-hyperintense foci were demonstrated more frequently within the plaques of symptomatic stenoses than within the plaques of asymptomatic stenoses (57.1 vs. 22%). The total wall thickness in the symptomatic stenoses was significantly higher than that seen in the asymptomatic stenoses. The stenosis grade for the BB-MRI was significantly correlated with the digital subtraction angiography grade. Conclusion: High-resolution, multicontrast-weighted BB-MRI has the potential to characterize atherosclerotic plaques in the MCA and may be a useful modality for evaluating the degree of stenosis.

Patterns of age-related water diffusion changes in human brain by concordance and discordance analysis

In diffusion tensor imaging (DTI), interpreting changes in terms of fractional anisotropy (FA) and mean diffusivity or axial (D(||)) and radial (D(⊥)) diffusivity can be ambiguous. The main objective of this study was to gain insight into the heterogeneity of age-related diffusion changes in human brain white matter by analyzing relationships between the diffusion measures in terms of concordance and discordance instead of evaluating them separately, which is difficult to interpret. Fifty-one cognitively normal subjects (22-79 years old) were studied with DTI at 4 Tesla. Age was associated with widespread concordant changes of decreased FA and increased MD but in some regions significant FA reductions occurred discordant to MD changes. Prominent age-related FA reductions were primarily related to greater radial (D(⊥)) than axial (D(||)) diffusivity changes, potentially reflecting processes of demyelination. In conclusion, concordant/discordant changes of DTI indices provide additional characterization of white matter alterations that accompany normal aging.

Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer's disease

In Alzheimers disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed.

An fMRI study of neuronal specificity of an acupoint: electroacupuncture stimulation of Yanglingquan (GB34) and its sham point.

The neuronal specificity of acupoints has not been entirely supported by the results of fMRI studies. The objective of this study was to investigate the neuronal specificity of an acupoint with electroacupuncture stimulation (EAS) using functional magnetic resonance imaging (fMRI). Functional MR imaging of the entire brain was performed in 12 normal healthy subjects during EAS of GB34 (Yanglingquan) and its sham point over the left leg in counter-balanced order. Anatomically, both GB34 and its sham point belong to the L5 spinal segment. EAS at the left GB34 specifically activated the right putamen, caudate body, claustrum, thalamus, cerebellum, as well as the left caudate body, ventral lateral thalamus, and cerebellum, all related to motor function. EAS at the sham point of the left GB34 specifically activated the right BA6, BA8, BA40, BA44, thalamus, as well as the left thalamus and cerebellum. Taken together, these findings suggest that EAS at an acupoint and its sham point, in the same spinal segment, induced specific cerebral response patterns. These findings support neuronal specificity of the acupoint studied. EAS at GB34 appears to be more related to motor function than EAS at its sham point, suggesting specificity of the GB34 acupoint. The results of this study provide neurobiological evidence for the existence of acupoint specificity, although further studies are necessary to better understand this phenomenon.

Pseudoprogression in patients with glioblastoma: added value of arterial spin labeling to dynamic susceptibility contrast perfusion MR imaging.

Background Pseudoprogression is a treatment-related reaction with an increase in contrast-enhancing lesion size, followed by subsequent improvement. Differentiating tumor recurrence from pseudoprogression remains a problem in neuro-oncology. Purpose To validate the added value of arterial spin labeling (ASL), compared with dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) alone, in distinguishing early tumor progression from pseudoprogression in patients with newly diagnosed glioblastoma multiforme (GBM). Material and Methods We retrospectively evaluated 117 consecutive patients with newly diagnosed GBM who underwent surgical resection and concurrent chemoradiotherapy (CCRT) as standard treatment modality. Sixty-two patients who developed contrast-enhancing lesions were assessed by both ASL and DSC perfusion MRI and classified into groups of early tumor recurrence (n = 34) or pseudoprogression (n = 28) based on pathologic analysis or clinical–radiologic follow-up. We used a qualitative analysis and semi-quantitative grade system on the basis of the tumor perfusion signal intensity into those equal to white matter (grade I), gray matter (grade II), and blood vessels (grade III) on ASL imaging. ASL grade was correlated with histogram parameters derived from DSC perfusion MRI. Results Pseudoprogression was observed in 15 (53.6%) patients with ASL grade I, 13 (46.4%) with grade II, and 0 (0%) with grade III, with early tumor progression observed in seven (20.6%) patients with ASL grade I, 11 (32.3%) with grade II, and 16 (47.1%) with grade III (P = 0.0022). DSC perfusion histogram parameters differed significantly among ASL grades. ASL grade was an independent predictor differentiating pseudoprogression from early tumor progression (odds ratio, 4.73; P = 0.0017). On qualitative review, adjunctive ASL produced eight (12.9%) more accurate results than DSC perfusion MRI alone. Conclusion ASL improves the diagnostic accuracy of DSC perfusion MRI in differentiating pseudoprogression from early tumor progression.

True Progression versus Pseudoprogression in the Treatment of Glioblastomas: A Comparison Study of Normalized Cerebral Blood Volume and Apparent Diffusion Coefficient by Histogram Analysis

Objective The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. Materials and Methods Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm2). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Students t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters. Results The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 × 10-6 mm2/sec for observer 1 and 907 × 10-6 mm2/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99). Conclusion The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas.

Perfusion magnetic resonance imaging: a comprehensive update on principles and techniques.

Perfusion is a fundamental biological function that refers to the delivery of oxygen and nutrients to tissue by means of blood flow. Perfusion MRI is sensitive to microvasculature and has been applied in a wide variety of clinical applications, including the classification of tumors, identification of stroke regions, and characterization of other diseases. Perfusion MRI techniques are classified with or without using an exogenous contrast agent. Bolus methods, with injections of a contrast agent, provide better sensitivity with higher spatial resolution, and are therefore more widely used in clinical applications. However, arterial spin-labeling methods provide a unique opportunity to measure cerebral blood flow without requiring an exogenous contrast agent and have better accuracy for quantification. Importantly, MRI-based perfusion measurements are minimally invasive overall, and do not use any radiation and radioisotopes. In this review, we describe the principles and techniques of perfusion MRI. This review summarizes comprehensive updated knowledge on the physical principles and techniques of perfusion MRI.