[Show abstract][Hide abstract] ABSTRACT: Vascular aging consists of complex and multifaceted processes that may be influenced by genetic polymorphisms of the renin-angiotensin system. A polymorphism in the angiotensin II type 1 receptor gene (AGTR1/rs5186) has been associated with an increased risk for arterial stiffness, hypertension, and ischemic stroke. Despite these identified relationships, the impact of AGTR1 A1166C on white matter integrity and cognition is less clear in a healthy aging population. The present study utilized indices of neuroimaging and neuropsychological assessment to examine the impact of the A1166C polymorphism on subcortical hyperintensities (SH) and cognition in 49 healthy adults between ages 51-85. Using a dominant statistical model (CC + CA (risk) vs. AA), results revealed significantly larger SH volume for individuals with the C1166 variant (p < 0.05, partial eta(2) = 0.117) compared with those with the AA genotype. Post hoc analyses indicated that increased SH volume in C allele carriers could not be explained by vascular factors such as pulse pressure or body mass index. In addition, cognitive performance did not differ significantly between groups and was not significantly associated with SH in this cohort. Results suggest that presence of the C1166 variant may serve as a biomarker of risk for suboptimal brain integrity in otherwise healthy older adults prior to changes in cognition.
Age (Dordrecht, Netherlands). 08/2014; 36(4):9664.
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship between older age and mean cerebral white matter fiber bundle lengths (FBLs) in specific white matter tracts in the brain using quantified diffusion MRI.METHODS: Sixty-three healthy adults older than 50 years underwent diffusion tensor imaging. Tractography tracings of cerebral white matter fiber bundles were derived from the diffusion tensor imaging data.RESULTS: Results revealed significantly shorter FBLs in the anterior thalamic radiation for every 1-year increase over the age of 50 years.CONCLUSIONS: We investigated the effects of age on FBL in specific white matter tracts in the brains of healthy older individuals utilizing quantified diffusion MRI. The results revealed a significant inverse relationship between age and FBL. Longitudinal studies of FBL across a lifespan are needed to examine the specific changes to the integrity of white matter.
[Show abstract][Hide abstract] ABSTRACT: Increased body mass index (BMI) has been linked to various detrimental health outcomes, including cognitive dysfunction. Recent work investigating associations between obesity and the brain has revealed decreased white matter microstructural integrity in individuals with elevated BMI, independent of age or comorbid health conditions. However, the relationship between high BMI and white matter fiber bundle length (FBL), which represents a novel metric of microstructural brain integrity, remains unknown. The present study utilized quantitative tractography based on diffusion tensor imaging (DTI) to investigate the relationship between BMI and FBL in 72 otherwise healthy older adults (24 males, 48 females). All participants were between 51 and 85 years of age (M = 63.26, SD = 8.76). Results revealed that elevated BMI was associated with shorter FBL in the temporal lobe, independent of age (p < .01). In addition, increased age was associated with shorter frontal, temporal, and whole brain FBL (all p values < .01). These findings indicate that, while increased age is an important factor associated with reduced FBL, high BMI is uniquely associated with reduced FBL in the temporal lobe. These data offer evidence for additive adverse effects of high BMI on the brain, especially in areas already vulnerable to aging processes and age-related neurodegenerative diseases. Further research is necessary to determine the physiological mechanisms associated with the shortening of FBL in individuals with high BMI.
Brain Imaging and Behavior 04/2013; · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The epsilon 4 (e4) isoform of apolipoprotein E (ApoE) is a known genetic risk factor for suboptimal brain health. Morphometry studies of brains with Alzheimer's disease have reported significant alterations in temporal lobe brain structure of e4 carriers, yet it remains unclear if the presence of an e4 allele is associated with alterations in the microstructure of white matter fiber bundles in healthy populations. The present study used quantitative tractography based on diffusion tensor imaging (qtDTI) to examine the influence of the e4 allele on temporal lobe fiber bundle lengths (FBLs) in 64 healthy older adults with at least one e4 allele (carriers, N = 23) versus no e4 allele (non-carriers, N = 41). Subtests from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also analyzed to examine memory performance between groups. Analyses revealed shorter FBLs in the left uncinate fasciculus (UF) (p = .038) of e4 carriers compared to non-carriers. By contrast, neither FBLs specific to the temporal lobe nor memory performances differed significantly between groups. Increased age correlated significantly with shorter FBL in the temporal lobe and UF, and with decreased performance on tests of memory. This is the first study to utilize qtDTI to examine relationships between FBL and ApoE genotype. Results suggest that FBL in the UF is influenced by the presence of an ApoE e4 allele (ApoE4) in healthy older adults. Temporal lobe FBLs, however, are more vulnerable to aging than the presence of an e4 allele.
Brain Imaging and Behavior 03/2013; · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: MRI studies of autism typically span years, may be longitudinal, and may involve multiple institutions. To reduce variability, a stable scanning environment across time and sites is essential. However, changes in scanner software can be frequent. MRI vendors provide software changes nearly annually, which can provide new scanning routines, but can also change existing routines and prevent operation of custom procedures. Conflicts can arise between changing-versus-maintaining scanner software. Changing software is typically desired by clinicians (diagnosis does not require stability); vendors (minimizing supported software levels); and some researchers who want to begin new studies. Maintaining software is typically desired by researchers who have ongoing studies or use custom procedures.
Objectives: These competing needs could be met by "dual booting", where the operator chooses the software level for booting the scanner. However, dual-booting is not commercially available on any FDA-approved MRI scanner. While dual-booting is done in the factory during software development, it is unclear whether an entire installed scanner can be seamlessly switched between two software environments. We aimed to develop dual-booting at a second scanning site to expand enrollment in our studies of autism and other disorders, while preserving ongoing longitudinal studies.
Methods: We devised procedures to dual-boot a Siemens 3T Allegra scanner at a second site (Pittsburgh; va30 software) to match the primary site (St.Louis; va25 software). The scanner has a host computer (running the scanner) and an imager computer (reconstructing images). Host and imager hardware/software differ between environments. To preserve scanning conditions, we used separate computers for va25 booting. The original va25 computers were recovered/tested at the second site, and rebuilt by replacing missing/unreliable components. We reinstalled all original va25 firmware/software, and moved the single-user license dongle from va30 to va25 host computer. After the stand-alone va25 host/imager were running, we plugged them into a network switch and set internal/external IP addresses. All communication errors resolved upon rebooting. We then connected the va25 computers to the scanner network by switching all cabling between va30/va25 computers, and then powering up the scanner. The va25 computers and all electronics booted up in the va25 environment, without errors.
Results: After booting under va25, we tuned the scanner using vendor procedures, storing tune settings on the va25 host. All performance specifications were met. Autism scan protocols ran seamlessly without modification, and image quality was excellent. The full switching procedure (scanner power-off, computer switching, scanner rebooting) takes only 13-15 minutes, during which the participant can be taken out of the scanner and the next participant prepared. For ongoing longitudinal studies, the scanner is run under va30 (using va30 tuning settings) to maintain those study conditions.
Conclusions: A dual-boot MRI environment can be used with longitudinal/multi-site autism studies to stabilize scanning conditions. Such studies are crucial to understanding brain developmental trajectory and biological heterogeneity in autism, which require long-term stability and large sample sizes. Setting up dual-booting requires a site willing to take risks/provide access; motivated/experienced investigators; available prior computers/software/manuals; and minimal scanner hardware changes.
Funding: MH090494; NS052470; AS03799; BC073839.
2012 International Meeting for Autism Research; 05/2012
[Show abstract][Hide abstract] ABSTRACT: The Montreal Cognitive Assessment (MoCA) screen was developed as a brief instrument to identify mild cognitive impairment and dementia among older individuals. To date, limited information is available regarding the neuroimaging signatures associated with performance on the scale, or the relationship between the MoCA and more comprehensive cognitive screening measures. The present study examined performances on the MoCA among 111 non-clinical older adults (ages 51-85) enrolled in a prospective study of cognitive aging. Participants were administered the MoCA, Mini-Mental State Exam (MMSE), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A subset of participants (N = 69) underwent structural 3 T magnetic resonance imaging (MRI) to define the volumes of total frontal gray matter, total hippocampus, T2-weighted subcortical hyperintensities (SH), and total brain volume. The results revealed significant correlations between the total score on the MoCA and total score on the RBANS and MMSE, though the strength of the correlations was more robust between the MoCA and the RBANS. Modest correlations between individual subscales of the MoCA and neuroimaging variables were evident, but no patterns of shared variance emerged between the MoCA total score and neuroimaging indices. In contrast, total brain volume correlated significantly with total score on the RBANS. These results suggest that additional studies are needed to define the significance of MoCA scores relative to brain integrity among an older population.
Archives of Clinical Neuropsychology 06/2011; 26(5):454-60. · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Recognition of faces/face emotions is commonly impaired in autism. Using DTT, we identified previously-unknown hippocampo-fusiform (HF) and amygdalo-fusiform (AF) face processing pathways (Smith et.al., 2009, JMRI). We found reduced minimum-diffusivity (D-min, intrinsic across-fiber diffusivity; Smith et.al., 2009) in right HF and right AF in autism, which correlated with decreased ability to recognize faces and their emotional content on neuropsychological tests (NPTs) (Conturo et.al., 2008, JINS; Conturo et.al., IMFAR2010). Such D-min reductions and DTT-NPT relationships suggest a new mechanism of autism -- small diameter axons that cause slowed neural transmission. This biologic mechanism is also consistent with: small cell bodies in hippocampus (Bauman et.al., 2005) and minicolumns (Casanova et.al., 2002); reduced fMRI correlations (Just et.al., 2004; Kleinhans et.al., 2008); lengthened reaction times (Townsend et.al., 1996); slowed electrophysiology (McPartland et.al., 2004); and symptom abatement with fever (Curran et.al., 2007).
Objectives: To confirm DTT-NPT relationships and devise a network model of slowed pathway transmission causing decreased ability to recognize faces/face emotions.
Methods: DTT data acquired in adolescent/adults with high-functioning autism meeting ADOS/ADI criteria were compared to additional NPT data acquired using sensitive custom tests of face-gender (Wilkinson et.al., IMFAR2009) and face-emotion (Rump et.al., 2009) recognition. A network model was developed accordingly.
Results: The gender/emotion NPTs showed a strong associated between lower performance and lower pathway D-min for both right HF/AF pathways (e.g., r=0.589; AF vs. face-gender NPT). These results confirm that the D-min reduction in autism-vs-controls in (Conturo, et al., 2008) is functionally significant, with the unusual reversal of the expected DTT-NPT relation supporting the small-diameter mechanism. The behavioral effects can be explained by a network model. Face visual-feature information first enters primary visual cortex (V1), then passes through the ventral-stream processing stages to arrive at fusiform face area. We posit a parallel passage of face information from V1 to amygdala [via the amygdalo-calcarine pathway in (Lori et.al., 2002)] to fusiform (via AF pathway). This parallel path is analogous to the putative "short-cut" of Rudrauf et.al. (2008) where visual information takes a short-cut to fusiform. In our model, emotional modulation of face perception occurs by visual information passing from V1 to amygdala and then to fusiform, arriving in fusiform at the same time (or earlier) that feature information arrives via ventral stream. If the AF were slowed by small-diameter axons (as in autism), emotion information would arrive at fusiform too late to modulate the featural information arriving from ventral stream, as that information would have already exited to other brain areas. A similar path involves hippocampus for memory modulation.
Conclusions: The association between decreased D-min in right HF/AF, and decreased recognition of faces/face emotions in autism, can be explained by small-diameter axons and slowed transmission in right HF/AF, combined with a network model whereby slowed transmission causes memory/emotional information to arrive at fusiform too late to modulate face information arriving via ventral stream.
Funding: NIH MH090494; Autism Speaks AS03799; The Nancy Lurie Marks Family Foundation; ACE HD055748; NS039538; DC006691.
International Meeting for Autism Research 2011; 05/2011
[Show abstract][Hide abstract] ABSTRACT: Multiple studies suggest that the corpus callosum in patients with autism is reduced in size. This study attempts to elucidate the nature of this morphometric abnormality by analyzing the shape of this structure in 17 high-functioning patients with autism and an equal number of comparison participants matched for age, sex, IQ, and handedness. The corpus callosum was segmented from T1 weighted images acquired with a Siemens 1.5 T scanner. Transformed coordinates of the curvilinear axis were aggregated into a parametric map and compared across series to derive regions of statistical significance. Our results indicate that a reduction in size of the corpus callosum occurs over all of its subdivisions (genu, body, splenium) in patients with autism. Since the commissural fibers that traverse the different anatomical compartments of the corpus callosum originate in disparate brain regions our results suggest the presence of widely distributed cortical abnormalities in people with autism.
[Show abstract][Hide abstract] ABSTRACT: The anterior limb of the internal capsule (ALIC) is a white matter structure, the medial portion of which includes the anterior thalamic radiation (ATR) carrying nerve fibers between thalamus and prefrontal cortex. ATR abnormalities have a possible link with cognitive abnormalities and negative symptoms in schizophrenia. We aimed to study the fiber integrity of the ATR more selectively by isolating the medial portion of the ALIC using region-of-interest based methodology. Diffusion-tensor imaging was used to measure the anisotropy of total ALIC (tALIC) and medial ALIC (mALIC) in 39 schizophrenia and 33 control participants, matched for age/gender/handedness. Relationships between anisotropy, psychopathology, and cognitive performance were analyzed. Compared with controls, schizophrenia participants had 4.55% lower anisotropy in right tALIC, and 5.38% lower anisotropy in right mALIC. There were no significant group anisotropy differences on the left. Significant correlations were observed between right ALIC integrity and relevant domains of cognitive function (e.g., executive function, working memory). Our study suggests an asymmetric microstructural change in ALIC in schizophrenia involving the right side, which is only minimally stronger in mALIC, and which correlates with cognitive impairment. Microstructural changes in the ALIC may be linked to cognitive dysfunction in schizophrenia.
Psychiatry Research 08/2010; 183(2):144-50. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Multiple neuroimaging studies of the corpus callosum have suggested the presence of morphometric abnormalities in autistic patients. There is at present a convergence of findings from structural studies indicating that any significant abnormality is always manifested as a smaller corpus callosum. This applies to both areal (i.e., single midsaggital measures) and volumetric assessments. The fact that the corpus callosum is smaller in autism is all the more striking when considering that total brain size appears, on average, to be increased.
Objectives: The study aimed to elucidate the nature of the corpus callosum abnormality in autism. It complemented previous morphometric studies by quantitating the shape of the corpus callosum boundary.
Methods: Seventeen high-functioning, autistic individuals were recruited (fourteen male, three female, all between 16 and 51 years of age). An equal number of non-autistic control subjects were enrolled, matched pairwise by age and sex with the autistic participants. T1-weighted images were acquired with Siemens MAGNETOM Vision 1.5 T scanners using an MPRAGE acquisition sequence. The corpus callosum was segmented from each image using a probabilistic model for corpus callosum shape. Boundary surfaces of the segmented corpora callosa were mapped into a standardized pseudocylindrical coordinate system (z, φ, ρ) to facilitate their comparison with each other. For each point z along a curvilinear axis from the genu to the splenium, and for each angle φ measured clockwise about this axis from anatomical right, ρ(z, φ) is the perpendicular distance from the axis to the boundary surface. The transformed surfaces were aggregated pointwise into a statistical parametric map of pairwise t statistics with 16 degrees of freedom. Regions of statistically significance were derived from the associated P-values using the method of Benjamini and Hochberg with a false discovery rate q* = 0.05.
Results: White matter in autism was reduced bilaterally along the body of the corpus callosum, apart from an increase in the region proximal to the right cingulate gyrus. There was also a reduction at the extreme posterior end of the structure. There was otherwise no significant difference around the mid-sagittal plane.
Conclusions: Results from our study indicate a generalized reduction of the corpus callosum in autism. The findings acquire relevance from previous neuroimaging studies that varied among themselves in regards to a preferred anatomical subdivision (e.g., genu, body, splenium). Generalized findings, involving the rostro-caudal extent of the corpus callosum, is expected from a mechanism involving corticalization, i.e. a mitotic event affecting periventricular germinal cells and the total number of cortical minicolumns.
International Meeting for Autism Research 2010; 05/2010
[Show abstract][Hide abstract] ABSTRACT: Background: Recognition of faces/face emotions is commonly impaired in adults/children with autism. Given the importance of face processing in autism, the ability to measure face-processing pathways with DTT (Smith et.al., 2009, JMRI), and the potential of pathway abnormalities to produce strong behavioral effects, we tested for abnormalities in face-processing pathways in autism. In an initial study (Conturo et.al., 2008, JINS), the right hippocampo-fusiform (HF) pathway involved in face recognition had reduced minimum-diffusivity (D-min, intrinsic across-fiber diffusivity; Smith et.al., 2009).
Objectives: Characterize/interpret DTT abnormalities in face-processing pathways by comparison to sensitive neuropsychological tests (NPTs).
Methods: Custom diffusion-tensor MRI data were acquired in 17 participants with high-functioning autism meeting ADOS/ADI criteria (age 16-53) and 17 individually-matched controls from 2002-2006. For comparison, we acquired sensitive custom NPTs of: face-memory (Best et.al., IMFAR2009); face-gender identification (Wilkinson et.al., IMFAR2009); and face-emotion recognition (Rump et.al., 2009) in the autism participants. We also examined the relationship to symptom severity during development as measured by the ADI.
Results: Autism participants were separated into lower/higher face-recognition subgroups using face-memory and Benton NPTs. The lower-performance subgroup had significantly slower D-min in both right HF (p = 0.019) and right amygdalo-fusiform (AF) pathway (p = 0.011). Gender/emotion NPTs showed a strong relation to DTT for both right HF/AFpathways. The DTT-NPT correlation was very high (e.g., r = 0.995/0.463 without/with one outlier; AF vs. face-gender NPT). All NPTs showed the same relation of slower D-min with lower performance for both pathways, indicating that the D-min reduction in autism-vs-controls described in (Conturo, et al., 2008) is functionally significant. The unusual reversal of the expected DTT-NPT relation supports a mechanism of small-diameter axons in right AF/HF. This interpretation parsimoniously accounts for the reversed DTT-NPT relation because small-diameter axons have slower transmission speed. This biologic mechanism is also consistent with: small cell bodies in hippocampus (Bauman et.al., 2005) and minicolumns (Casanova et.al., 2002); reduced fMRI correlations (Just et.al., 2004; Kleinhans et.al., 2008); lengthened reaction times (Townsend et.al., 1996); slowed electrophysiology (McPartland et.al., 2004); and symptom abatement with fever (Curran et.al., 2007). A correlation between ADI, Section A (reciprocal social interactions) and right HF D-min (r = -0.413; p = 0.047; slower D-min associated with childhood social impairment) suggests an early-developmental process, consistent with known impairments in face processing in young children. The D-min reduction is unlikely to be due to intervening variables (e.g., behavioral therapy) since participants do not report any consistent therapy. Any therapy effects would thus average out (and would oppose the reversed DTT-NPT relation). Finally, the high DTT-NPT correlation suggests that axonal diameter is a strong determinant of function, despite intervening variables. [More subtle secondary changes can occur in left AF/HF (Conturo et.al, 2008), consistent with relative sparing of object processing in autism (Humphreys et.al., 2008).]
Conclusions: A strong association between decreased D-min and decreased function (as measured by behavioral NPTs) occurred in right AF/HF in autism, supporting a mechanism of small-diameter axons. A similar DTT-ADI relation was found, suggesting that this mechanism occurs in childhood, and persists into adulthood.
International Meeting for Autism Research 2010; 05/2010
[Show abstract][Hide abstract] ABSTRACT: To use MRI diffusion-tensor tracking (DTT) to test for the presence of unknown neuronal fiber pathways interconnecting the mid-fusiform cortex and anteromedial temporal lobe in humans. Such pathways are hypothesized to exist because these regions coactivate in functional MRI (fMRI) studies of emotion-valued faces and words, suggesting a functional link that could be mediated by neuronal connections.
A total of 15 normal human subjects were studied using unbiased DTT approaches designed for probing unknown pathways, including whole-brain seeding and large pathway-selection volumes. Several quality-control steps verified the results.
Parallel amygdalo-fusiform and hippocampo-fusiform pathways were found in all subjects. The pathways begin/end at the mid-fusiform gyrus above the lateral occipitotemporal sulcus bilaterally. The superior pathway ends/begins at the superolateral amygdala. The inferior pathway crosses medially and ends/begins at the hippocampal head. The pathways are left-lateralized, with consistently larger cross-sectional area, higher anisotropy, and lower minimum eigenvalue (D-min) on the left, where D-min assesses intrinsic cross-fiber diffusivity independent of curvature.
A previously-undescribed pathway system interconnecting the mid-fusiform region with the amygdala/hippocampus has been revealed. This pathway system may be important for recognition, memory consolidation, and emotional modulation of face, object, and lexical information, which may be disrupted in conditions such as Alzheimer's disease.
Journal of Magnetic Resonance Imaging 06/2009; 29(6):1248-61. · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reaction time (RT) is one of the most widely used measures of performance in experimental psychology, yet relatively few fMRI studies have included trial-by-trial differences in RT as a predictor variable in their analyses. Using a multi-study approach, we investigated whether there are brain regions that show a general relationship between trial-by-trial RT variability and activation across a range of cognitive tasks.
The relation between trial-by-trial differences in RT and brain activation was modeled in five different fMRI datasets spanning a range of experimental tasks and stimulus modalities. Three main findings were identified. First, in a widely distributed set of gray and white matter regions, activation was delayed on trials with long RTs relative to short RTs, suggesting delayed initiation of underlying physiological processes. Second, in lateral and medial frontal regions, activation showed a "time-on-task" effect, increasing linearly as a function of RT. Finally, RT variability reliably modulated the BOLD signal not only in gray matter but also in diffuse regions of white matter.
The results highlight the importance of modeling trial-by-trial RT in fMRI analyses and raise the possibility that RT variability may provide a powerful probe for investigating the previously elusive white matter BOLD signal.
PLoS ONE 02/2009; 4(1):e4257. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: MRI diffusion-tensor tracking (DTT) was performed in 17 high-functioning adolescents/adults with autism and 17 pairwise-matched controls. White matter pathways involved in face processing were examined due to the relevance of face perception to the social symptoms of autism, and due to known behavioral and functional imaging findings in autism. The hippocampo-fusiform (HF) and amygdalo-fusiform (AF) pathways had normal size and shape but abnormal microstructure in the autism group. The right HF had reduced across-fiber diffusivity (D-min) compared with controls, opposite to the whole-brain effect of increased D-min. In contrast, left HF, right AF, and left AF had increased D-min and increased along-fiber diffusivity (D-max), more consistent with the whole-brain effect. There was a general loss of lateralization compared with controls. The right HF D-min was markedly low in the autism subgroup with lower Benton face recognition scores, compared with the lower-Benton control subgroup, and compared with the higher-Benton autism subgroup. Similar behavioral relationships were found for performance IQ. Such results suggest an early functionally-significant pathological process in right HF consistent with small-diameter axons (with correspondingly slower neural transmission) and/or higher packing density. In left AF and HF, changes were interpreted as secondary, possibly reflecting axonal loss and/or decreased myelination.
Journal of the International Neuropsychological Society 12/2008; 14(6):933-46. · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine optimal conditions for precise measurement of arterial input function (AIFs) in dynamic susceptibility contrast (DSC) perfusion MRI.
Magnitude-based (DeltaR(2)*) and phase-based (Deltaphi) AIFs were numerically simulated for several doses and baseline MRI noise levels [SNR(I(0))]. Random noise (1000 realizations) was added to real/imaginary MRI signals (derived from an internal carotid AIF), and AIF signal, noise, and signal-to-noise ratio (SNR) were determined. The optimal dose was defined as the dose that maximizes mean AIF SNR over the first-pass (SNR(mean)), rather than SNR at the AIF peak (SNR(peak)) because, compared to SNR(peak), doses predicted by SNR(mean) reduced the AIF-induced variability in cerebral blood flow (CBF) by 24% to 40%.
The AIF SNR is most influenced by choice of AIF signal, then optimal dosing, each with little penalty. Compared to DeltaR(2)*, Deltaphi signal has 4 to 80 times the SNR over all doses and time points, and approximately 10-fold SNR(mean) at respective optimal doses. Optimal doses induce 85% to 90% signal drop for the DeltaR(2)* method, and 70% to 75% for Deltaphi, with two-fold dose errors causing approximately 1.7-fold loss in SNR(mean). Increases in SNR(I(0)) proportionally increase AIF SNR, but at a cost.
AIF SNR is affected most by signal type, then dosing, and lastly, SNR(I(0)).
Journal of Magnetic Resonance Imaging 04/2007; 25(3):598-611. · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cerebral perfusion imaging using dynamic susceptibility contrast (DSC) has been the subject of considerable research and shows promise for basic science and clinical use. In DSC, the MRI signals in brain tissue and feeding arteries are monitored dynamically in response to a bolus injection of paramagnetic agents, such as gadolinium (Gd) chelates. DSC has the potential to allow quantitative imaging of parameters such as cerebral blood flow (CBF) with a high signal-to-noise ratio (SNR) in a short scan time; however, quantitation depends critically on accurate and precise measurement of the arterial input function (AIF). We discuss many requirements and factors that make it difficult to measure the AIF. The AIF signal should be linear with respect to Gd concentration, convertible to the same concentration scale as the tissue signal, and independent of hematocrit. Complicated relationships between signal and concentration can violate these requirements. The additional requirements of a high SNR and high spatial/temporal resolution are technically challenging. AIF measurements can also be affected by signal saturation and aliasing, as well as dispersion/delay between the AIF sampling site and the tissue. We present new in vivo preliminary results for magnitude-based (DeltaR2*) and phase-based (Deltaphi) AIF measurements that show a linearity advantage of phase, and a disparity in the scaling of Deltaphi AIFs, DeltaR2* AIFs, and DeltaR2* tissue curves. Finally, we discuss issues related to the choice of AIF signal for quantitative perfusion imaging.
Journal of Magnetic Resonance Imaging 01/2006; 22(6):697-703. · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: After a decade of evolution and application of diffusion imaging, a large body of literature has been accumulated. It is in this context that the accuracy and precision of diffusion-weighted and quantitative diffusion MRI are reviewed. The emphasis of the review is on practical methods for clinical human imaging, particularly in the brain. The requirements for accuracy and precision are reviewed for various clinical and basic science applications. The methods of measuring and calculating diffusion effects with MRI are reviewed. The pulse gradient spin echo (PGSE) methods are emphasized as these methods are used most commonly in the clinical setting. Processing of PGSE data is reviewed. Various PGSE encoding schemes are also reviewed in terms of the accuracy and precision of isotropic and anisotropic diffusion measurements. The broad range of factors impacting the accuracy of the PGSE methods and other encoding schemes is then considered. Firstly, system inaccuracies such as background imaging gradients, gradient linearity, refocusing RF pulses, eddy currents, image misregistration, noise and dynamic range are considered. A second class of inaccuracies is contributed by the bulk effects of the imaged object, and include sample background gradients, subject motion of cerebrospinal fluid and organs, and aperiodic organ motion. A final category of potential inaccuracies is classified as being contributed by microscopic, biophysical tissue properties and include partial volume effects, anisotropy, restriction, diffusion distance, compartmentation, exchange, multiexponential diffusion decay, T2 weighting and microvascular perfusion. Finally, the application of diffusion methods to studies of blood flow in the microvasculature (i.e. the arterioles, capillaries and venules) are reviewed in detail, particularly in terms of feasibility and the stringent accuracy and precision requirements. Recent provocative studies examining the use of PGSE approaches to suppress microvascular signals in brain functional MRI (fMRI) are also reviewed.