Comparison of CE-FDG-PET/CT with CE-FDG-PET/MR in the evaluation of osseous metastases in breast cancer patients.

BACKGROUND: Despite improvements in treatments, metastatic breast cancer remains difficult to cure. Bones constitute the most common site of first-time recurrence, occurring in 40-75% of cases. Therefore, evaluation for possible osseous metastases is crucial. Technetium 99 ((99)Tc) bone scintigraphy and fluorodexossyglucose (FDG) positron emission tomography (PET)-computed tomography (PET-CT) are the most commonly used techniques to assess osseous metastasis. PET magnetic resonance (PET-MR) imaging is an innovative technique still under investigation. We compared the capability of PET-MR to that of same-day PET-CT to assess osseous metastases in patients with breast cancer. METHODS: One hundred and nine patients with breast cancer, who underwent same-day contrast enhanced (CE)-PET-CT and CE-PET-MR, were evaluated. CE-PET-CT and CE-PET-MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Binomial confidence intervals and a χ(2) test were used for categorical data, and paired t-test was used for the SUVmax data; a non-informative prior Bayesian approach was used to estimate and compare the specificities. RESULTS: Osseous metastases affected 25 out 109 patients. Metastases were demonstrated by CE-PET-CT in 22 out of 25 patients (88%±7%), and by CE-PET-MR in 25 out of 25 patients (100%). CE-PET-CT revealed 90 osseous metastases and CE-PET-MR revealed 141 osseous metastases (P<0.001). The estimated sensitivity of CE-PET-CT and CE-PET-MR were 0.8519 and 0.9630, respectively. The estimated specificity for CE-FDG-PET-MR was 0.9884. The specificity of CE-PET-CT cannot be determined from patient-level data, because CE-PET-CT yielded a false-positive lesion in a patient who also had other, true metastases. CONCLUSIONS: CE-PET-MR detected a higher number of osseous metastases than did same-day CE-PET-CT, and was positive for 12% of the patients deemed osseous metastasis-negative on the basis of CE-PET-CT.

The imagined itch: brain circuitry supporting nocebo-induced itch in atopic dermatitis patients.

BACKGROUND: Psychological factors are known to significantly modulate itch in patients suffering from chronic itch. Itch is also highly susceptible to both placebo and nocebo (negative placebo) effects. Brain activity likely supports nocebo-induced itch, but is currently unknown. METHODS: We collected functional MRI (fMRI) data from atopic dermatitis (AD) patients, in a within-subject design, and contrast brain response to nocebo saline understood to be allergen vs open-label saline control. Exploratory analyses compared results to real allergen itch response and placebo responsiveness, evaluated in the same patients. RESULTS: Nocebo saline produced greater itch than open saline control (P < 0.01). Compared to open saline, nocebo saline demonstrated greater fMRI response in caudate, dorsolateral prefrontal cortex (dlPFC), and intraparietal sulcus (iPS) - brain regions important for cognitive executive and motivational processing. Exploratory analyses found that subjects with greater dlPFC and caudate activation to nocebo-induced itch also demonstrated greater dlPFC and caudate activation, respectively, for real allergen itch. Subjects reporting greater nocebo-induced itch also demonstrated greater placebo reduction of allergen-evoked itch, suggesting increased generalized modulation of itch perception. CONCLUSIONS: Our study demonstrates the capacity of nocebo saline to mimic both the sensory and neural effects of real allergens and provides an insight to the brain mechanisms supporting nocebo-induced itch in AD, thus aiding our understanding of the role that expectations and other psychological factors play in modulating itch perception in chronic itch patients.

Pushing the limits of in vivo diffusion MRI for the Human Connectome Project.

Perhaps more than any other "-omics" endeavor, the accuracy and level of detail obtained from mapping the major connection pathways in the living human brain with diffusion MRI depend on the capabilities of the imaging technology used. The current tools are remarkable; allowing the formation of an "image" of the water diffusion probability distribution in regions of complex crossing fibers at each of half a million voxels in the brain. Nonetheless our ability to map the connection pathways is limited by the image sensitivity and resolution, and also the contrast and resolution in encoding of the diffusion probability distribution. The goal of our Human Connectome Project (HCP) is to address these limiting factors by re-engineering the scanner from the ground up to optimize the high b-value, high angular resolution diffusion imaging needed for sensitive and accurate mapping of the brain's structural connections. Our efforts were directed based on the relative contributions of each scanner component. The gradient subsection was a major focus since gradient amplitude is central to determining the diffusion contrast, the amount of T2 signal loss, and the blurring of the water PDF over the course of the diffusion time. By implementing a novel 4-port drive geometry and optimizing size and linearity for the brain, we demonstrate a whole-body sized scanner with G(max) = 300 mT/m on each axis capable of the sustained duty cycle needed for diffusion imaging. The system is capable of slewing the gradient at a rate of 200 T/m/s as needed for the EPI image encoding. In order to enhance the efficiency of the diffusion sequence we implemented a FOV shifting approach to Simultaneous MultiSlice (SMS) EPI capable of unaliasing 3 slices excited simultaneously with a modest g-factor penalty allowing us to diffusion encode whole brain volumes with low TR and TE. Finally we combine the multi-slice approach with a compressive sampling reconstruction to sufficiently undersample q-space to achieve a DSI scan in less than 5 min. To augment this accelerated imaging approach we developed a 64-channel, tight-fitting brain array coil and show its performance benefit compared to a commercial 32-channel coil at all locations in the brain for these accelerated acquisitions. The technical challenges of developing the over-all system are discussed as well as results from SNR comparisons, ODF metrics and fiber tracking comparisons. The ultra-high gradients yielded substantial and immediate gains in the sensitivity through reduction of TE and improved signal detection and increased efficiency of the DSI or HARDI acquisition, accuracy and resolution of diffusion tractography, as defined by identification of known structure and fiber crossing.

T2* mapping and B0 orientation-dependence at 7 T reveal cyto- and myeloarchitecture organization of the human cortex.

Ultra-high field MRI (≥ 7 T) has recently shown great sensitivity to depict patterns of tissue microarchitecture. Moreover, recent studies have demonstrated a dependency between T2* and orientation of white matter fibers with respect to the main magnetic field B0. In this study we probed the potential of T2* mapping at 7 T to provide new markers of cortical architecture. We acquired multi-echo measurements at 7 T and mapped T2* over the entire cortex of eight healthy individuals using surface-based analysis. B0 dependence was tested by computing the angle θ(z) between the normal of the surface and the direction of B0, then fitting T2*(θ(z)) using model from the literature. Average T2* in the cortex was 32.20 +/- 1.35 ms. Patterns of lower T2* were detected in the sensorimotor, visual and auditory cortices, likely reflecting higher myelin content. Significantly lower T2* was detected in the left hemisphere of the auditory region (p<0.005), suggesting higher myelin content, in accordance with previous investigations. B0 orientation dependence was detected in some areas of the cortex, the strongest being in the primary motor cortex (∆R2*=4.10 Hz). This study demonstrates that quantitative T2* measures at 7 T MRI can reveal patterns of cytoarchitectural organization of the human cortex in vivo and that B0 orientation dependence can probe the coherency and orientation of gray matter fibers in the cortex, shedding light into the potential use of this type of contrast to characterize cyto-/myeloarchitecture and to understand the pathophysiology of diseases associated with changes in iron and/or myelin concentration.

In vivo evidence of disseminated subpial T2* signal changes in multiple sclerosis at 7 T: a surface-based analysis.

Cortical subpial demyelination is frequent in multiple sclerosis (MS) and is closely associated with disease progression and poor neurological outcome. Although cortical lesions have been difficult to detect using conventional MRI, preliminary data using T2*-weighted imaging at ultra-high field 7T MRI showed improved sensitivity for detecting and categorizing different histological types of cortical MS lesions. In this study we combined high-resolution 7T MRI with a surface-based analysis technique to quantify and map subpial T2*-weighted signal changes in seventeen patients with MS. We applied a robust method to register 7T data with the reconstructed cortical surface of each individual and used a general linear model to assess in vivo an increase in subpial T2*-weighted signal in patients versus age-matched controls, and to investigate the spatial distribution of cortical subpial changes across the cortical ribbon. We also assessed the relationship between subpial T2* signal changes at 7T, Expanded Disability Status Scale (EDSS) score and white matter lesion load (WMLL). Patients with MS showed significant T2*-weighted signal increase in the frontal lobes (parsopercularis, precentral gyrus, middle and superior frontal gyrus, orbitofrontal cortex), anterior cingulate, temporal (superior, middle and inferior temporal gyri), and parietal cortices (superior and inferior parietal cortex, precuneus), but also in occipital regions of the left hemisphere. We found significant correlations between subpial T2*-weighted signal and EDSS score in the precentral gyrus (ρ=0.56, P=0.02) and between T2*-weighted signal and WMLL in the lateral orbitofrontal, superior parietal, cuneus, precentral and superior frontal regions. Our data support the presence of disseminated subpial increases in T2* signal in subjects with MS, which may reflect the diffuse subpial pathology described in neuropathology.

QUantitative Imaging of eXtraction of oxygen and TIssue consumption (QUIXOTIC) using venular-targeted velocity-selective spin labeling.

While oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO(2)) are fundamental parameters of brain health and function, a robust MRI-based mapping of OEF and CMRO(2) amenable to functional MRI (fMRI) has not been established. To address this issue, a novel method called QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption, or QUIXOTIC, is introduced. The key innovation in QUIXOTIC is the use of velocity-selective spin labeling to isolate MR signal exclusively from postcapillary venular blood on a voxel-by-voxel basis. Measuring the T(2) of this venular-targeted blood allows calibration to venular oxygen saturation (Y(v)) via theoretical and experimental T(2) versus blood oxygen saturation relationships. Y(v) is converted to OEF, and baseline CMRO(2) is subsequently estimated from OEF and additional cerebral blood flow and hematocrit measurements. Theory behind the QUIXOTIC technique is presented, and implications of cutoff velocity (V(CUTOFF)) and outflow time parameters are discussed. Cortical gray matter values obtained with QUIXOTIC in 10 healthy volunteers are Y(v) = 0.73 ± 0.02, OEF = 0.26 ± 0.02, and CMRO(2) = 125 ± 15 µmol/100 g min. Results are compared to global measures obtained with the T(2) relaxation under spin tagging (TRUST) technique. The preliminary data presented suggest that QUIXOTIC will be useful for mapping Y(v), OEF, and CMRO(2), in both clinical and functional MRI settings.

Reef coral from aldabra: new mode of reproduction.

A unique mode of asexual reproduction in recently collected specimens of Goniopora (Scleractinia) is reported. Skeleton is absent from new polyps; the skelton develops independently of the parent colony as the new polyps themselves increase. The young colonies eventually become detached. The cycle seems to be a response to a sandy habitat, a conclusion reached by analogy With Fungia and Manicina.

Borders of multiple visual areas in humans revealed by functional magnetic resonance imaging.

The borders of human visual areas V1, V2, VP, V3, and V4 were precisely and noninvasively determined. Functional magnetic resonance images were recorded during phase-encoded retinal stimulation. This volume data set was then sampled with a cortical surface reconstruction, making it possible to calculate the local visual field sign (mirror image versus non-mirror image representation). This method automatically and objectively outlines area borders because adjacent areas often have the opposite field sign. Cortical magnification factor curves for striate and extrastriate cortical areas were determined, which showed that human visual areas have a greater emphasis on the center-of-gaze than their counterparts in monkeys. Retinotopically organized visual areas in humans extend anteriorly to overlap several areas previously shown to be activated by written words.

Functional mapping of the human visual cortex by magnetic resonance imaging.

Knowledge of regional cerebral hemodynamics has widespread application for both physiological research and clinical assessment because of the well-established interrelation between physiological function, energy metabolism, and localized blood supply. A magnetic resonance technique was developed for quantitative imaging of cerebral hemodynamics, allowing for measurement of regional cerebral blood volume during resting and activated cognitive states. This technique was used to generate the first functional magnetic resonance maps of human task activation, by using a visual stimulus paradigm. During photic stimulation, localized increases in blood volume (32 +/- 10 percent, n = 7 subjects) were detected in the primary visual cortex. Center-of-mass coordinates and linear extents of brain activation within the plane of the calcarine fissure are reported.

Building memories: remembering and forgetting of verbal experiences as predicted by brain activity.

A fundamental question about human memory is why some experiences are remembered whereas others are forgotten. Brain activation during word encoding was measured using blocked and event-related functional magnetic resonance imaging to examine how neural activation differs for subsequently remembered and subsequently forgotten experiences. Results revealed that the ability to later remember a verbal experience is predicted by the magnitude of activation in left prefrontal and temporal cortices during that experience. These findings provide direct evidence that left prefrontal and temporal regions jointly promote memory formation for verbalizable events.

Projective imaging of pulsatile flow with magnetic resonance.

Noninvasive angiography with magnetic resonance is demonstrated. Signal arising in all structures except vessels that carry pulsatile flow is eliminated by means of velocity-dependent phase contrast, electrocardiographic gating, and image subtraction. Background structures become in effect transparent, enabling the three-dimensional vascular tree to be imaged by projection to a two-dimensional image plane. Image acquisition and processing are accomplished with entirely conventional two-dimensional Fourier transform magnetic resonance imaging techniques. When imaged at 0.6 tesla, vessels 1 to 2 millimeters in diameter are routinely detected in a 50-centimeter field of view with data acquisition times less than 15 minutes. Studies of normal and pathologic anatomy are illustrated in human subjects.

Comparison of CBF Measured with Combined Velocity-Selective Arterial Spin-Labeling and Pulsed Arterial Spin-Labeling to Blood Flow Patterns Assessed by Conventional Angiography in Pediatric Moyamoya.

BACKGROUND AND PURPOSE: Imaging CBF is important for managing pediatric moyamoya. Traditional arterial spin-labeling MR imaging detects delayed transit thorough diseased arteries but is inaccurate for measuring perfusion because of these delays. Velocity-selective arterial spin-labeling is insensitive to transit delay and well-suited for imaging Moyamoya perfusion. This study assesses the accuracy of a combined velocity-selective arterial spin-labeling and traditional pulsed arterial spin-labeling CBF approach in pediatric moyamoya, with comparison to blood flow patterns on conventional angiography. MATERIALS AND METHODS: Twenty-two neurologically stable pediatric patients with moyamoya and 5 asymptomatic siblings without frank moyamoya were imaged with velocity-selective arterial spin-labeling, pulsed arterial spin-labeling, and DSA (patients). Qualitative comparison was performed, followed by a systematic comparison using ASPECTS-based scoring. Quantitative pulsed arterial spin-labeling CBF and velocity-selective arterial spin-labeling CBF for the middle cerebral artery, anterior cerebral artery, and posterior cerebral artery territories were also compared. RESULTS: Qualitatively, velocity-selective arterial spin-labeling perfusion maps reflect the DSA parenchymal phase, regardless of postinjection timing. Conversely, pulsed arterial spin-labeling maps reflect the DSA appearance at postinjection times closer to the arterial spin-labeling postlabeling delay, regardless of vascular phase. ASPECTS comparison showed excellent agreement (88%, κ = 0.77, P < .001) between arterial spin-labeling and DSA, suggesting velocity-selective arterial spin-labeling and pulsed arterial spin-labeling capture key perfusion and transit delay information, respectively. CBF coefficient of variation, a marker of perfusion variability, was similar for velocity-selective arterial spin-labeling in patient regions of delayed-but-preserved perfusion compared to healthy asymptomatic sibling regions (coefficient of variation = 0.30 versus 0.26, respectively, Δcoefficient of variation = 0.04), but it was significantly different for pulsed arterial spin-labeling (coefficient of variation = 0.64 versus 0.34, Δcoefficient of variation = 0.30, P < .001). CONCLUSIONS: Velocity-selective arterial spin-labeling offers a powerful approach to image perfusion in pediatric moyamoya due to transit delay insensitivity. Coupled with pulsed arterial spin-labeling for transit delay information, a volumetric MR imaging approach capturing key DSA information is introduced.

Voluntary attention modulates fMRI activity in human MT-MST.

How does voluntary attention to one attribute of a visual stimulus affect the neural processing of that stimulus? We used functional magnetic resonance imaging to examine the attentional modulation of neural activity in the human homolog of the MT-MST complex, which is known to be involved in the processing of visual motion. Using a visual stimulus containing both moving and stationary dots, we found significantly more MT-MST activation when subjects attended to the moving dots than when they attended to the stationary dots, even though the visual stimulus was identical during the two conditions.

Response and habituation of the human amygdala during visual processing of facial expression.

We measured amygdala activity in human volunteers during rapid visual presentations of fearful, happy, and neutral faces using functional magnetic resonance imaging (fMRI). The first experiment involved a fixed order of conditions both within and across runs, while the second one used a fully counterbalanced order in addition to a low level baseline of simple visual stimuli. In both experiments, the amygdala was preferentially activated in response to fearful versus neutral faces. In the counterbalanced experiment, the amygdala also responded preferentially to happy versus neutral faces, suggesting a possible generalized response to emotionally valenced stimuli. Rapid habituation effects were prominent in both experiments. Thus, the human amygdala responds preferentially to emotionally valenced faces and rapidly habituates to them.

Cortical mechanisms specific to explicit visual object recognition.

The cortical mechanisms associated with conscious object recognition were studied using functional magnetic resonance imaging (fMRI). Participants were required to recognize pictures of masked objects that were presented very briefly, randomly and repeatedly. This design yielded a gradual accomplishment of successful recognition. Cortical activity in a ventrotemporal visual region was linearly correlated with perception of object identity. Therefore, although object recognition is rapid, awareness of an object's identity is not a discrete phenomenon but rather associated with gradually increasing cortical activity. Furthermore, the focus of the activity in the temporal cortex shifted anteriorly as subjects reported an increased knowledge regarding identity. The results presented here provide new insights into the processes underlying explicit object recognition, as well as the analysis that takes place immediately before and after recognition is possible.

Visual motion processing investigated using contrast agent-enhanced fMRI in awake behaving monkeys.

To reduce the information gap between human neuroimaging and macaque physiology and anatomy, we mapped fMRI signals produced by moving and stationary stimuli (random dots or lines) in fixating monkeys. Functional sensitivity was increased by a factor of approximately 5 relative to the BOLD technique by injecting a contrast agent (monocrystalline iron oxide nanoparticle [MION]). Areas identified as motion sensitive included V2, V3, MT/V5, vMST, FST, VIP, and FEF (with moving dots), as well as V4, TE, LIP, and PIP (with random lines). These regions sensitive for moving dots are largely in agreement with monkey single unit data and (except for V3A) with human fMRI results. Moving lines activate some regions that have not been previously implicated in motion processing. Overall, the results clarify the relationship between the motion pathway and the dorsal stream in primates.

Acute effects of cocaine on human brain activity and emotion.

We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while subjects rated scales for rush, high, low, and craving. Cocaine induced focal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus, cingulate, lateral prefrontal and temporal cortices, parietal cortex, striate/extrastriate cortices, ventral tegmentum, and pons and produced signal decreases in amygdala, temporal pole, and medial frontal cortex. Saline produced few positive or negative activations, which were localized to lateral prefrontal cortex and temporo-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might reflect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These included the ventral tegmentum, pons, basal forebrain, caudate, cingulate, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correlated with craving than with rush ratings; such regions included the NAc/SCC, right parahippocampal gyrus, and some regions of lateral prefrontal cortex. Sustained negative signal change was noted in the amygdala, which correlated with craving ratings. Our data demonstrate the ability of fMRI to map dynamic patterns of brain activation following cocaine infusion in cocaine-dependent subjects and provide evidence of dynamically changing brain networks associated with cocaine-induced euphoria and cocaine-induced craving.

In vivo quantification of transvascular water exchange during the acute phase of permanent stroke.

Mechanisms that underlie early ischemic damages to the blood-brain-barrier (BBB) are not well understood. This study presents a novel magnetic resonance imaging (MRI) technique using a widely available pulse sequence and a long-circulating intravascular contrast agent to quantify water movements across the BBB at early stages of stroke progression. We characterized the integrity of the BBB by measuring the flip angle dependence of the water exchange-affected MRI signal intensity, to generate an efficient quantitative index of vascular permeability (WEI, or water exchange index). We performed in vivo MRI experiments to measure the transvascular WEI immediately after the permanent filament occlusion of the middle cerebral artery of mice (n = 5), in which we monitored changes in blood volume (V(b)), apparent diffusion coefficient (ADC), and intra-/extravascular WEI for 4 hours. Statistically significant elevations (P < 0.05) of WEI in the ischemic tissue were observed as early as 1 hour after ischemic onset. Initial reduction of the apparent blood volume (V(app)) in the infarct cortex was followed by a continuous increase of V(app) over time. Although the measured ADC in the ipsilesional cortex continuously decreased, the abnormally high intra-/extravascular WEI remained constant at a significantly elevated level, indicating apparent BBB injury at this early stage of stroke.

Diagnostic Performance of a 10-Minute Gadolinium-Enhanced Brain MRI Protocol Compared with the Standard Clinical Protocol for Detection of Intracranial Enhancing Lesions.

BACKGROUND AND PURPOSE: The development of new MR imaging scanners with stronger gradients and improvement in coil technology, allied with emerging fast imaging techniques, has allowed a substantial reduction in MR imaging scan times. Our goal was to develop a 10-minute gadolinium-enhanced brain MR imaging protocol with accelerated sequences and to evaluate its diagnostic performance compared with the standard clinical protocol. MATERIALS AND METHODS: Fifty-three patients referred for brain MR imaging with contrast were scanned with a 3T scanner. Each MR image consisted of 5 basic fast precontrast sequences plus standard and accelerated versions of the same postcontrast T1WI sequences. Two neuroradiologists assessed the image quality and the final diagnosis for each set of postcontrast sequences and compared their performances. RESULTS: The acquisition time of the combined accelerated pre- and postcontrast sequences was 10 minutes and 15 seconds; and of the fast postcontrast sequences, 3 minutes and 36 seconds, 46% of the standard sequences. The 10-minute postcontrast axial T1WI had fewer image artifacts (P < .001) and better overall diagnostic quality (P < .001). Although the 10-minute MPRAGE sequence showed a tendency to have more artifacts than the standard sequence (P = .08), the overall diagnostic quality was similar (P = .66). Moreover, there was no statistically significant difference in the diagnostic performance between the protocols. The sensitivity, specificity, and accuracy values for the 10-minute protocol were 100.0%, 88.9%, and 98.1%. CONCLUSIONS: The 10-minute brain MR imaging protocol with contrast is comparable in diagnostic performance with the standard protocol in an inpatient motion-prone population, with the additional benefits of reducing acquisition times and image artifacts.

Cyclic Vomiting Syndrome is characterized by altered functional brain connectivity of the insular cortex: A cross-comparison with migraine and healthy adults.

Cyclic Vomiting Syndrome (CVS) has been linked to episodic migraine, yet little is known about the precise brain-based mechanisms underpinning CVS, and whether these associated conditions share similar pathophysiology. We investigated the functional integrity of salience (SLN) and sensorimotor (SMN) intrinsic connectivity networks in CVS, migraine and healthy controls using brain functional Magnetic Resonance Imaging. CVS, relative to both migraine and controls, showed increased SLN connectivity to middle/posterior insula, a key brain region for nausea and viscerosensory processing. In contrast, this same region showed diminished SMN connectivity in both CVS and migraine. These results highlight both unique and potentially shared pathophysiology between these conditions, and suggest a potential target for therapeutics in future studies.