Publications by authors named "Bruce R Rosen"

171 Publications

PET/MRI assessment of lung nodules in primary abdominal malignancies: sensitivity and outcome analysis.

Eur J Nucl Med Mol Imaging 2021 Jan 7. Epub 2021 Jan 7.

Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, White 270, Boston, MA, 02114, USA.

Purpose: To evaluate PET/MR lung nodule detection compared to PET/CT or CT, to determine growth of nodules missed by PET/MR, and to investigate the impact of missed nodules on clinical management in primary abdominal malignancies.

Methods: This retrospective IRB-approved study included [18F]-FDG PET/MR in 126 patients. All had standard of care chest imaging (SCI) with diagnostic chest CT or PET/CT within 6 weeks of PET/MR that served as standard of reference. Two radiologists assessed lung nodules (size, location, consistency, position, and [18F]-FDG avidity) on SCI and PET/MR. A side-by-side analysis of nodules on SCI and PET/MR was performed. The nodules missed on PET/MR were assessed on follow-up SCI to ascertain their growth (≥ 2 mm); their impact on management was also investigated.

Results: A total of 505 nodules (mean 4 mm, range 1-23 mm) were detected by SCI in 89/126 patients (66M:60F, mean age 60 years). PET/MR detected 61 nodules for a sensitivity of 28.1% for patient and 12.1% for nodule, with higher sensitivity for > 7 mm nodules (< 30% and > 70% respectively, p < 0.05). 75/337 (22.3%) of the nodules missed on PET/MR (follow-up mean 736 days) demonstrated growth. In patients positive for nodules at SCI and negative at PET/MR, missed nodules did not influence patients' management.

Conclusions: Sensitivity of lung nodule detection on PET/MR is affected by nodule size and is lower than SCI. 22.3% of missed nodules increased on follow-up likely representing metastases. Although this did not impact clinical management in study group with primary abdominal malignancy, largely composed of extra-thoracic advanced stage cancers, with possible different implications in patients without extra-thoracic spread.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-020-05113-1DOI Listing
January 2021

Vascular dysfunction promotes regional hypoxia after bevacizumab therapy in recurrent glioblastoma patients.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa157. Epub 2020 Nov 17.

Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Hypoxia is a driver of treatment resistance in glioblastoma. Antiangiogenic agents may transiently normalize blood vessels and decrease hypoxia before excessive pruning of vessels increases hypoxia. The time window of normalization is dose and time dependent. We sought to determine how VEGF blockade with bevacizumab modulates tumor vasculature and the impact that those vascular changes have on hypoxia in recurrent glioblastoma patients.

Methods: We measured tumor volume, vascular permeability (Ktrans), perfusion parameters (cerebral blood flow/volume, vessel caliber, and mean transit time), and regions of hypoxia in patients with recurrent glioblastoma before and after treatment with bevacizumab alone or with lomustine using [F]FMISO PET-MRI. We also examined serial changes in plasma biomarkers of angiogenesis and inflammation.

Results: Eleven patients were studied. The magnitude of global tumor hypoxia was variable across these 11 patients prior to treatment and it did not significantly change after bevacizumab. The hypoxic regions had an inefficient vasculature characterized by elevated cerebral blood flow/volume and increased vessel caliber. In a subset of patients, there were tumor subregions with decreased mean transit times and a decrease in hypoxia, suggesting heterogeneous improvement in vascular efficiency. Bevacizumab significantly changed known pharmacodynamic biomarkers such as plasma VEGF and PlGF.

Conclusions: The vascular signature in hypoxic tumor regions indicates a disorganized vasculature which, in most tumors, does not significantly change after bevacizumab treatment. While some tumor regions showed improved vascular efficiency following treatment, bevacizumab did not globally alter hypoxia or normalize tumor vasculature in glioblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/noajnl/vdaa157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764510PMC
November 2020

Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients.

Front Neurol 2020 3;11:590573. Epub 2020 Dec 3.

Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States.

Oxidative stress and protein aggregation are key mechanisms in amyotrophic lateral sclerosis (ALS) disease. Reduced glutathione (GSH) is the most important intracellular antioxidant that protects neurons from reactive oxygen species. We hypothesized that levels of GSH measured by MR spectroscopic imaging (MRSI) in the motor cortex and corticospinal tract are linked to clinical trajectory of ALS patients. Investigate the value of GSH imaging to probe clinical decline of ALS patients in combination with other neurochemical and structural parameters. Twenty-four ALS patients were imaged at 3 T with an advanced MR protocol. Mapping GSH levels in the brain is challenging, and for this purpose, we used an optimized spectral-edited 3D MRSI sequence with real-time motion and field correction to image glutathione and other brain metabolites. In addition, our imaging protocol included (i) an adiabatic T1ρ sequence to image macromolecular fraction of brain parenchyma, (ii) diffusion tensor imaging (DTI) for white matter tractography, and (iii) high-resolution anatomical imaging. We found GSH in motor cortex ( = -0.431, = 0.04) and corticospinal tract ( = -0.497, = 0.016) inversely correlated with time between diagnosis and imaging. N-Acetyl-aspartate (NAA) in motor cortex inversely correlated ( = -0.416, = 0.049), while mean water diffusivity ( = 0.437, = 0.033) and T1ρ ( = 0.482, = 0.019) positively correlated with disease progression measured by imputed change in revised ALS Functional Rating Scale. There is more decrease in the motor cortex than in the white matter for GSH compared to NAA, glutamate, and glutamine. Our study suggests that a panel of biochemical and structural imaging biomarkers defines a brain endophenotype, which can be used to time biological events and clinical progression in ALS patients. Such a quantitative brain endophenotype may stratify ALS patients into more homogeneous groups for therapeutic interventions compared to clinical criteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.590573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744722PMC
December 2020

History of conditioned reward association disrupts inhibitory control: an examination of neural correlates.

Neuroimage 2021 02 13;227:117629. Epub 2020 Dec 13.

University of North Carolina at Chapel Hill, Psychology and Neuroscience Department, 235 E. Cameron Street, Chapel Hill, NC 27599, United States; Boston Children's Hospital at Harvard Medical School, United States.

The neural processes that support inhibitory control in the face of stimuli with a history of reward association are not yet well understood. Yet, the ability to flexibly adapt behavior to changing reward-contingency contexts is important for daily functioning and warrants further investigation. This study aimed to characterize neural and behavioral impacts of stimuli with a history of conditioned reward association on motor inhibitory control in healthy young adults by investigating group-level effects as well as individual variation in the ability to inhibit responses to stimuli with a reward history. Participants (N = 41) first completed a reward conditioning phase, during which responses to rewarded stimuli were associated with money and responses to unrewarded stimuli were not. Rewarded and unrewarded stimuli from training were carried forward as No-Go targets in a subsequent go/no-go task to test the effect of reward history on inhibitory control. Participants underwent functional brain imaging during the go/no-go portion of the task. On average, a history of reward conditioning disrupted inhibitory control. Compared to inhibition of responses to stimuli with no reward history, trials that required inhibition of responses to previously rewarded stimuli were associated with greater activity in frontal and striatal regions, including the inferior frontal gyrus, insula, striatum, and thalamus. Activity in the insula and thalamus during false alarms and in the ventromedial prefrontal cortex during correctly withheld trials predicted behavioral performance on the task. Overall, these results suggest that reward history serves to disrupt inhibitory control and provide evidence for diverging roles of the insula and ventromedial prefrontal cortex while inhibiting responses to stimuli with a reward history.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2020.117629DOI Listing
February 2021

Examining cognitive control and reward interactions in adolescent externalizing symptoms.

Dev Cogn Neurosci 2020 10 8;45:100813. Epub 2020 Jul 8.

Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

During adolescence, rapid development and reorganization of the dopaminergic system supports increasingly sophisticated reward learning and the ability to exert behavioral control. Disruptions in the ability to exert control over previously rewarded behavior may underlie some forms of adolescent psychopathology. Specifically, symptoms of externalizing psychopathology may be associated with difficulties in flexibly adapting behavior in the context of reward. However, the direct interaction of cognitive control and reward learning in adolescent psychopathology symptoms has not yet been investigated. The present study used a Research Domain Criteria framework to investigate whether behavioral and neuronal indices of inhibition to previously rewarded stimuli underlie individual differences in externalizing symptoms in N = 61 typically developing adolescents. Using a task that integrates the Monetary Incentive Delay and Go-No-Go paradigms, we observed a positive association between externalizing symptoms and activation of the left middle frontal gyrus during response inhibition to cues with a history of reward. These associations were robust to controls for internalizing symptoms and neural recruitment during inhibition of cues with no reward history. Our findings suggest that inhibitory control over stimuli with a history of reward may be a useful marker for future inquiry into the development of externalizing psychopathology in adolescence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dcn.2020.100813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387777PMC
October 2020

Dynamic brain-body coupling of breath-by-breath O2-CO2 exchange ratio with resting state cerebral hemodynamic fluctuations.

PLoS One 2020 21;15(9):e0238946. Epub 2020 Sep 21.

Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.

Background: The origin of low frequency cerebral hemodynamic fluctuations (CHF) in the resting state remains unknown. Breath-by breath O2-CO2 exchange ratio (bER) has been reported to correlate with the cerebrovascular response to brief breath hold challenge at the frequency range of 0.008-0.03Hz in healthy adults. bER is defined as the ratio of the change in the partial pressure of oxygen (ΔPO2) to that of carbon dioxide (ΔPCO2) between end inspiration and end expiration. In this study, we aimed to investigate the contribution of respiratory gas exchange (RGE) metrics (bER, ΔPO2 and ΔPCO2) to low frequency CHF during spontaneous breathing.

Methods: Twenty-two healthy adults were included. We used transcranial Doppler sonography to evaluate CHF by measuring the changes in cerebral blood flow velocity (ΔCBFv) in bilateral middle cerebral arteries. The regional CHF were mapped with blood oxygenation level dependent (ΔBOLD) signal changes using functional magnetic resonance imaging. Temporal features and frequency characteristics of RGE metrics during spontaneous breathing were examined, and the simultaneous measurements of RGE metrics and CHF (ΔCBFv and ΔBOLD) were studied for their correlation.

Results: We found that the time courses of ΔPO2 and ΔPCO2 were interdependent but not redundant. The oscillations of RGE metrics were coherent with resting state CHF at the frequency range of 0.008-0.03Hz. Both bER and ΔPO2 were superior to ΔPCO2 in association with CHF while CHF could correlate more strongly with bER than with ΔPO2 in some brain regions. Brain regions with the strongest coupling between bER and ΔBOLD overlapped with many areas of default mode network including precuneus and posterior cingulate.

Conclusion: Although the physiological mechanisms underlying the strong correlation between bER and CHF are unclear, our findings suggest the contribution of bER to low frequency resting state CHF, providing a novel insight of brain-body interaction via CHF and oscillations of RGE metrics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238946PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505589PMC
October 2020

The Mind of a Mouse.

Cell 2020 Sep;182(6):1372-1376

Neuroscience Department, Washington University School of Medicine, St. Louis, MO, USA.

Large scientific projects in genomics and astronomy are influential not because they answer any single question but because they enable investigation of continuously arising new questions from the same data-rich sources. Advances in automated mapping of the brain's synaptic connections (connectomics) suggest that the complicated circuits underlying brain function are ripe for analysis. We discuss benefits of mapping a mouse brain at the level of synapses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2020.08.010DOI Listing
September 2020

Axon diameter index estimation independent of fiber orientation distribution using high-gradient diffusion MRI.

Neuroimage 2020 11 1;222:117197. Epub 2020 Aug 1.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States; Harvard Medical School, Boston, MA, United States; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States.

Axon diameter mapping using high-gradient diffusion MRI has generated great interest as a noninvasive tool for studying trends in axonal size in the human brain. One of the main barriers to mapping axon diameter across the whole brain is accounting for complex white matter fiber configurations (e.g., crossings and fanning), which are prevalent throughout the brain. Here, we present a framework for generalizing axon diameter index estimation to the whole brain independent of the underlying fiber orientation distribution using the spherical mean technique (SMT). This approach is shown to significantly benefit from the use of real-valued diffusion data with Gaussian noise, which reduces the systematic bias in the estimated parameters resulting from the elevation of the noise floor when using magnitude data with Rician noise. We demonstrate the feasibility of obtaining whole-brain orientationally invariant estimates of axon diameter index and relative volume fractions in six healthy human volunteers using real-valued diffusion data acquired on a dedicated high-gradient 3-Tesla human MRI scanner with 300 mT/m maximum gradient strength. The trends in axon diameter index are consistent with known variations in axon diameter from histology and demonstrate the potential of this generalized framework for revealing coherent patterns in axonal structure throughout the living human brain. The use of real-valued diffusion data provides a viable solution for eliminating the Rician noise floor and should be considered for all spherical mean approaches to microstructural parameter estimation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2020.117197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736138PMC
November 2020

Intact Brain Network Function in an Unresponsive Patient with COVID-19.

Ann Neurol 2020 10 6;88(4):851-854. Epub 2020 Aug 6.

Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Although several structural brain abnormalities have been described, their impact on brain function and implications for prognosis are unknown. Functional neuroimaging, which has prognostic significance, has yet to be explored in this population. Here we describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated intact functional network connectivity, and weeks later recovered the ability to follow commands. When prognosticating for survivors of severe COVID-19, clinicians should consider that brain networks may remain functionally intact despite structural injury and prolonged unresponsiveness. ANN NEUROL 2020;88:851-854.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361474PMC
October 2020

Consensus recommendations for a dynamic susceptibility contrast MRI protocol for use in high-grade gliomas.

Neuro Oncol 2020 09;22(9):1262-1275

Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Despite the widespread clinical use of dynamic susceptibility contrast (DSC) MRI, DSC-MRI methodology has not been standardized, hindering its utilization for response assessment in multicenter trials. Recently, the DSC-MRI Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition issued an updated consensus DSC-MRI protocol compatible with the standardized brain tumor imaging protocol (BTIP) for high-grade gliomas that is increasingly used in the clinical setting and is the default MRI protocol for the National Clinical Trials Network. After reviewing the basis for controversy over DSC-MRI protocols, this paper provides evidence-based best practices for clinical DSC-MRI as determined by the Committee, including pulse sequence (gradient echo vs spin echo), BTIP-compliant contrast agent dosing (preload and bolus), flip angle (FA), echo time (TE), and post-processing leakage correction. In summary, full-dose preload, full-dose bolus dosing using intermediate (60°) FA and field strength-dependent TE (40-50 ms at 1.5 T, 20-35 ms at 3 T) provides overall best accuracy and precision for cerebral blood volume estimates. When single-dose contrast agent usage is desired, no-preload, full-dose bolus dosing using low FA (30°) and field strength-dependent TE provides excellent performance, with reduced contrast agent usage and elimination of potential systematic errors introduced by variations in preload dose and incubation time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523451PMC
September 2020

Reduced tactile acuity in chronic low back pain is linked with structural neuroplasticity in primary somatosensory cortex and is modulated by acupuncture therapy.

Neuroimage 2020 08 5;217:116899. Epub 2020 May 5.

Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA; Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. Electronic address:

Prior studies have shown that patients suffering from chronic Low Back Pain (cLBP) have impaired somatosensory processing including reduced tactile acuity, i.e. reduced ability to resolve fine spatial details with the perception of touch. The central mechanism(s) underlying reduced tactile acuity are unknown but may include changes in specific brain circuitries (e.g. neuroplasticity in the primary somatosensory cortex, S1). Furthermore, little is known about the linkage between changes in tactile acuity and the amelioration of cLBP by somatically-directed therapeutic interventions, such as acupuncture. In this longitudinal neuroimaging study, we evaluated healthy control adults (HC, N ​= ​50) and a large sample of cLBP patients (N ​= ​102) with structural brain imaging (T1-weighted MRI for Voxel-Based Morphometry, VBM; Diffusion Tensor Imaging, DTI) and tactile acuity testing using two-point discrimination threshold (2PDT) over the lower back (site of pain) and finger (control) locations. Patients were evaluated at baseline and following a 4-week course of acupuncture, with patients randomized to either verum acupuncture, two different forms of sham acupuncture (designed with or without somatosensory afference), or no-intervention usual care control. At baseline, cLBP patients demonstrated reduced acuity (greater 2PDT, P ​= ​0.01) over the low back, but not finger (P ​= ​0.29) locations compared to HC, suggesting that chronic pain affects tactile acuity specifically at body regions encoding the experience of clinical pain. At baseline, Gray Matter Volume (GMV) was elevated and Fractional Anisotropy (FA) was reduced, respectively, in the S1-back region of cLBP patients compared to controls (P ​< ​0.05). GMV in cLBP correlated with greater 2PDT-back scores (ρ ​= ​0.27, P ​= ​0.02). Following verum acupuncture, tactile acuity over the back was improved (reduced 2PDT) and greater improvements were associated with reduced S1-back GMV (ρ ​= ​0.52, P ​= ​0.03) and increased S1-back adjacent white matter FA (ρ ​= ​-0.56, P ​= ​0.01). These associations were not seen for non-verum control interventions. Thus, S1 neuroplasticity in cLBP is linked with deficits in tactile acuity and, following acupuncture therapy, may represent early mechanistic changes in somatosensory processing that track with improved tactile acuity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2020.116899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395964PMC
August 2020

Cerebrovascular reactivity assessment with O2-CO2 exchange ratio under brief breath hold challenge.

PLoS One 2020 24;15(3):e0225915. Epub 2020 Mar 24.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.

Background: Hypercapnia during breath holding is believed to be the dominant driver behind the modulation of cerebral blood flow (CBF). However, increasing evidence show that mild hypoxia and mild hypercapnia in breath hold (BH) could work synergistically to enhance CBF response. We hypothesized that breath-by-breath O2-CO2 exchange ratio (bER), defined as the ratio of the change in partial pressure of oxygen (ΔPO2) to that of carbon dioxide (ΔPCO2) between end inspiration and end expiration, would be able to better correlate with the global and regional cerebral hemodynamic responses (CHR) to BH challenge. We aimed to investigate whether bER is a more useful index than end-tidal PCO2 to characterize cerebrovascular reactivity (CVR) under BH challenge.

Methods: We used transcranial Doppler ultrasound (TCD) to evaluate CHR under BH challenge by measuring cerebral blood flow velocity (CBFv) in the middle cerebral arteries. Regional changes in CHR to BH and exogenous CO2 challenges were mapped with blood oxygenation level dependent (BOLD) signal changes using functional magnetic resonance imaging (fMRI). We correlated respiratory gas exchange (RGE) metrics (bER, ΔPO2, ΔPCO2, end-tidal PCO2 and PO2, and time of breaths) with CHR (CBFv and BOLD) to BH challenge. Temporal features and frequency characteristics of RGE metrics and their coherence with CHR were examined.

Results: CHR to brief BH epochs and free breathing were coupled with both ΔPO2 and ΔPCO2. We found that bER was superior to either ΔPO2 or ΔPCO2 alone in coupling with the changes of CBFv and BOLD signals under breath hold challenge. The regional CVR results derived by regressing BOLD signal changes on bER under BH challenge resembled those derived by regressing BOLD signal changes on end-tidal PCO2 under exogenous CO2 challenge.

Conclusion: Our findings provide a novel insight on the potential of using bER to better quantify CVR changes under BH challenge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225915PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092994PMC
May 2020

Resting-state "physiological networks".

Neuroimage 2020 06 5;213:116707. Epub 2020 Mar 5.

Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA, USA.

Slow changes in systemic brain physiology can elicit large fluctuations in fMRI time series, which manifest as structured spatial patterns of temporal correlations between distant brain regions. Here, we investigated whether such "physiological networks"-sets of segregated brain regions that exhibit similar responses following slow changes in systemic physiology-resemble patterns associated with large-scale networks typically attributed to remotely synchronized neuronal activity. By analyzing a large group of subjects from the 3T Human Connectome Project (HCP) database, we demonstrate brain-wide and noticeably heterogenous dynamics tightly coupled to either respiratory variation or heart rate changes. We show, using synthesized data generated from physiological recordings across subjects, that these physiologically-coupled fluctuations alone can produce networks that strongly resemble previously reported resting-state networks, suggesting that, in some cases, the "physiological networks" seem to mimic the neuronal networks. Further, we show that such physiologically-relevant connectivity estimates appear to dominate the overall connectivity observations in multiple HCP subjects, and that this apparent "physiological connectivity" cannot be removed by the use of a single nuisance regressor for the entire brain (such as global signal regression) due to the clear regional heterogeneity of the physiologically-coupled responses. Our results challenge previous notions that physiological confounds are either localized to large veins or globally coherent across the cortex, therefore emphasizing the necessity to consider potential physiological contributions in fMRI-based functional connectivity studies. The rich spatiotemporal patterns carried by such "physiological" dynamics also suggest great potential for clinical biomarkers that are complementary to large-scale neuronal networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2020.116707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165049PMC
June 2020

Implementation and Validation of a Three-dimensional Cardiac Motion Estimation Network.

Radiol Artif Intell 2019 Jul 17;1(4):e180080. Epub 2019 Jul 17.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 149 13th St, Charlestown, MA 02129 (M.A.M., D.I.G., I.A., J.K.C., B.R.R., C.C.); Harvard-MIT Division of Health Sciences and Technology (M.A.M.) and Computer Science and Artificial Intelligence Laboratory (I.A.), Massachusetts Institute of Technology, Cambridge, Mass.

Purpose: To describe an unsupervised three-dimensional cardiac motion estimation network (CarMEN) for deformable motion estimation from two-dimensional cine MR images.

Materials And Methods: A function was implemented using CarMEN, a convolutional neural network that takes two three-dimensional input volumes and outputs a motion field. A smoothness constraint was imposed on the field by regularizing the Frobenius norm of its Jacobian matrix. CarMEN was trained and tested with data from 150 cardiac patients who underwent MRI examinations and was validated on synthetic ( = 100) and pediatric ( = 33) datasets. CarMEN was compared to five state-of-the-art nonrigid body registration methods by using several performance metrics, including Dice similarity coefficient (DSC) and end-point error.

Results: On the synthetic dataset, CarMEN achieved a median DSC of 0.85, which was higher than all five methods (minimum-maximum median [or MMM], 0.67-0.84; < .001), and a median end-point error of 1.7, which was lower than (MMM, 2.1-2.7; < .001) or similar to (MMM, 1.6-1.7; > .05) all other techniques. On the real datasets, CarMEN achieved a median DSC of 0.73 for Automated Cardiac Diagnosis Challenge data, which was higher than (MMM, 0.33; < .0001) or similar to (MMM, 0.72-0.75; > .05) all other methods, and a median DSC of 0.77 for pediatric data, which was higher than (MMM, 0.71-0.76; < .0001) or similar to (MMM, 0.77-0.78; > .05) all other methods. All values were derived from pairwise testing. For all other metrics, CarMEN achieved better accuracy on all datasets than all other techniques except for one, which had the worst motion estimation accuracy.

Conclusion: The proposed deep learning-based approach for three-dimensional cardiac motion estimation allowed the derivation of a motion model that balances motion characterization and image registration accuracy and achieved motion estimation accuracy comparable to or better than that of several state-of-the-art image registration algorithms.© RSNA, 2019
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/ryai.2019180080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677286PMC
July 2019

Blood Oxygen Level-Dependent MRI of the Myocardium with Multiecho Gradient-Echo Spin-Echo Imaging.

Radiology 2020 03 21;294(3):538-545. Epub 2020 Jan 21.

From the Departments of Radiology (M.v.d.B., G.J.H.S., N.H.J.P., R.J.H.B.) and Nuclear Medicine and Molecular Imaging (R.H.J.A.S.), University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging (M.v.d.B., M.K.M., S.H.H., D.E.S., C.C., B.R.R., C.T.N., K.S.), and Cardiovascular Research Center (D.E.S., C.T.N.), Massachusetts General Hospital, Harvard Medical School, Charlestown, Mass; Department of Diagnostic Physics, Oslo University Hospital, Oslo, Norway (K.E.E.); Department of Biomedical Photonic Imaging, University of Twente, Enschede, the Netherlands (R.H.J.A.S., R.J.H.B.); and Division of Health Sciences and Technology, Harvard-MIT, Cambridge, Mass (D.E.S., K.S.).

Background Myocardial oxygenation imaging could help determine the presence of microvascular dysfunction associated with increased cardiovascular risk. However, it is challenging to depict the potentially small oxygenation alterations with current noninvasive cardiac MRI blood oxygen level-dependent (BOLD) techniques. Purpose To demonstrate the cardiac application of a gradient-echo spin-echo (GESE) echo-planar imaging sequence for dynamic and quantitative heartbeat-to-heartbeat BOLD MRI and evaluate the sequence in populations both healthy and with hypertension in combination with a breath hold-induced CO intervention. Materials and Methods GESE echo-planar imaging sequence was performed in 18 healthy participants and in eight prospectively recruited participants with hypertension on a 3.0-T MRI system. T2 and T2* maps were calculated per heartbeat with a four-parameter fitting technique. Septal regions of interests were used to determine T2 and T2* values per heartbeat and examined over the course of a breath hold to determine BOLD changes. T2 and T2* changes of healthy participants and participants with hypertension were compared by using a nonparametric Mann-Whitney test. Results GESE echo-planar imaging approach gave spatially stable T2 and T2* maps per heartbeat for healthy participants and participants with hypertension, with mean T2 values of 43 msec ± 5 (standard deviation) and 46 msec ± 9, respectively, and mean T2* values of 28 msec ± 5 and 22 msec ± 5, respectively. The healthy participants exhibited increasing T2 and T2* values over the course of a breath hold with a mean positive slope of 0.2 msec per heartbeat ± 0.1 for T2 and 0.2 msec per heartbeat ± 0.1 for T2*, whereas for participants with hypertension these dynamic T2 and T2* values had a mean negative slope of -0.2 msec per heartbeat ± 0.2 for T2 and -0.1 msec per heartbeat ± 0.2 for T2*. The difference in these mean slopes between healthy participants and participants with hypertension was significant for both T2 ( < .001) and T2* ( < .001). Conclusion Gradient-echo spin-echo echo-planar imaging sequence provided quantitative T2 and T2* maps per heartbeat and enabled dynamic heartbeat-to-heartbeat blood oxygen level-dependent (BOLD)-response imaging by analyzing changes in T2 and T2* over the time of a breath-hold intervention. This approach could identify differences in the BOLD response between healthy participants and participants with hypertension. © RSNA, 2020 See also the editorial by Friedrich in this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2020191845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053244PMC
March 2020

Management implications of fluorodeoxyglucose positron emission tomography/magnetic resonance in untreated intrahepatic cholangiocarcinoma.

Eur J Nucl Med Mol Imaging 2020 07 8;47(8):1871-1884. Epub 2019 Nov 8.

Department of Radiology, Massachusetts General Hospital, Harvard Medical School, WHT 270, 55 Fruit St., Boston, MA, 02114, USA.

Purpose: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis with surgical resection offering the best chance for long-term survival and potential cure. However, in up to 36% of patients who undergo surgery, more extensive disease is found at time of operation requiring cancellation of surgery. PET/MR is a novel hybrid technology that might improve local and whole-body staging in ICC patients, potentially influencing clinical management. This study was aimed to investigate the possible management implications of PET/MR, relative to conventional imaging, in patients affected by untreated intrahepatic cholangiocarcinoma.

Methods: Retrospective review of the clinicopathologic features of 37 patients with iCCC, who underwent PET/MR between September 2015 and August 2018, was performed to investigate the management implications that PET/MR had exerted on the affected patients, relative to conventional imaging.

Results: Of the 37 patients enrolled, median age 63.5 years, 20 (54%) were female. The same day PET/CT was performed in 26 patients. All patients were iCCC-treatment-naïve. Conventional imaging obtained as part of routine clinical care demonstrated early-stage resectable disease for 15 patients and advanced stage disease beyond the scope of surgical resection for 22. PET/MR modified the clinical management of 11/37 (29.7%) patients: for 5 patients (13.5%), the operation was cancelled due to identification of additional disease, while 4 "inoperable" patients (10.8%) underwent an operation. An additional 2 patients (5.4%) had a significant change in their operative plan based on PET/MR.

Conclusions: When compared with standard imaging, PET/MR significantly influenced the treatment plan in 29.7% of patients with iCCC.

Trial Registration: 2018P001334.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-019-04558-3DOI Listing
July 2020

Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep.

Science 2019 11;366(6465):628-631

Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.

Sleep is essential for both cognition and maintenance of healthy brain function. Slow waves in neural activity contribute to memory consolidation, whereas cerebrospinal fluid (CSF) clears metabolic waste products from the brain. Whether these two processes are related is not known. We used accelerated neuroimaging to measure physiological and neural dynamics in the human brain. We discovered a coherent pattern of oscillating electrophysiological, hemodynamic, and CSF dynamics that appears during non-rapid eye movement sleep. Neural slow waves are followed by hemodynamic oscillations, which in turn are coupled to CSF flow. These results demonstrate that the sleeping brain exhibits waves of CSF flow on a macroscopic scale, and these CSF dynamics are interlinked with neural and hemodynamic rhythms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.aax5440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309589PMC
November 2019

Probabilistic Structural Atlas of the Inferior and Superior Colliculi, Medial and Lateral Geniculate Nuclei and Superior Olivary Complex in Humans Based on 7 Tesla MRI.

Front Neurosci 2019 7;13:764. Epub 2019 Aug 7.

Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, MGH and Harvard Medical School, Boston, MA, United States.

Despite extensive neuroimaging research of primary sensory cortices involved in auditory and visual functions, subcortical structures within these domains, such as the inferior and superior colliculi, the medial and lateral geniculate nuclei and the superior olivary complex, are currently understudied with magnetic resonance imaging (MRI) in living humans. This is because a precise localization of these nuclei is hampered by the limited contrast and sensitivity of conventional neuroimaging methods for deep brain nuclei. In this work, we used 7 Tesla multi-modal (T-weighted and diffusion fractional anisotropy) 1.1 mm isotropic resolution MRI to achieve high sensitivity and contrast for single-subject brainstem and thalamic nuclei delineation. After precise coregistration to stereotactic space, we generated an human probabilistic atlas of auditory (medial geniculate nucleus, inferior colliculus, and superior olivary complex) and visual (lateral geniculate nucleus and superior colliculus) subcortical nuclei. We foresee the use of this atlas as a tool to precisely identify the location and shape of auditory/visual deep nuclei in research as well as clinical human studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2019.00764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694208PMC
August 2019

Clinical impact of PET/MR in treated colorectal cancer patients.

Eur J Nucl Med Mol Imaging 2019 Oct 29;46(11):2260-2269. Epub 2019 Jul 29.

Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, White 270, Boston, MA, 02114, USA.

Purpose: The primary aim of the present study was to evaluate if PET/MR induced management changes versus standard of care imaging (SCI) in treated colorectal cancer patients. The secondary aim was to assess the staging performance of PET/MR and of SCI versus the final oncologic stage.

Methods: Treated CRC patients who underwent PET/MR with F-FDG and SCI between January 2016 and October 2018 were enrolled in this retrospective study. Their medical records were evaluated to ascertain if PET/MR had impacted on their clinical management versus SCI. The final oncologic stage, as reported in the electronic medical record, was considered the true stage of disease.

Results: A total of 39 patients who underwent 42 PET/MR studies were included, mean age 56.7 years (range 39-75 years), 26 males, and 13 females. PET/MR changed clinical management 15/42 times (35.7%, standard error ± 7.4%); these 15 changes in management were due to upstaging in 9/42 (21.5%) and downstaging in 6/42 (14.2%). The differences in management prompted by SCI versus PET/MR were statistically significant, and PET/MR outperformed SCI (P value < 0.001; odds ratio = 2.8). In relation to the secondary outcome, PET/MR outperformed the SCI in accuracy of oncologic staging (P value = 0.016; odds ratio = 4.6).

Conclusions: PET/MR is a promising imaging tool in the evaluation of treated CRC and might change the management in these patients. However, multicenter prospective studies with larger patient samples are required in order to confirm these preliminary results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-019-04449-7DOI Listing
October 2019

Publisher Correction: Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI.

Sci Rep 2019 Jun 14;9(1):8721. Epub 2019 Jun 14.

Stephen E. and Catherine Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-44365-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565804PMC
June 2019

Automatic assessment of glioma burden: a deep learning algorithm for fully automated volumetric and bidimensional measurement.

Neuro Oncol 2019 11;21(11):1412-1422

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: Longitudinal measurement of glioma burden with MRI is the basis for treatment response assessment. In this study, we developed a deep learning algorithm that automatically segments abnormal fluid attenuated inversion recovery (FLAIR) hyperintensity and contrast-enhancing tumor, quantitating tumor volumes as well as the product of maximum bidimensional diameters according to the Response Assessment in Neuro-Oncology (RANO) criteria (AutoRANO).

Methods: Two cohorts of patients were used for this study. One consisted of 843 preoperative MRIs from 843 patients with low- or high-grade gliomas from 4 institutions and the second consisted of 713 longitudinal postoperative MRI visits from 54 patients with newly diagnosed glioblastomas (each with 2 pretreatment "baseline" MRIs) from 1 institution.

Results: The automatically generated FLAIR hyperintensity volume, contrast-enhancing tumor volume, and AutoRANO were highly repeatable for the double-baseline visits, with an intraclass correlation coefficient (ICC) of 0.986, 0.991, and 0.977, respectively, on the cohort of postoperative GBM patients. Furthermore, there was high agreement between manually and automatically measured tumor volumes, with ICC values of 0.915, 0.924, and 0.965 for preoperative FLAIR hyperintensity, postoperative FLAIR hyperintensity, and postoperative contrast-enhancing tumor volumes, respectively. Lastly, the ICCs for comparing manually and automatically derived longitudinal changes in tumor burden were 0.917, 0.966, and 0.850 for FLAIR hyperintensity volume, contrast-enhancing tumor volume, and RANO measures, respectively.

Conclusions: Our automated algorithm demonstrates potential utility for evaluating tumor burden in complex posttreatment settings, although further validation in multicenter clinical trials will be needed prior to widespread implementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noz106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827825PMC
November 2019

Maturational Changes in Human Dorsal and Ventral Visual Networks.

Cereb Cortex 2019 12;29(12):5131-5149

Department of Radiology, MGH/MIT/HMS A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown MA 02129, USA.

Developmental neuroimaging studies report the emergence of increasingly diverse cognitive functions as closely entangled with a rise-fall modulation of cortical thickness (CTh), structural cortical and white-matter connectivity, and a time-course for the experience-dependent selective elimination of the overproduced synapses. We examine which of two visual processing networks, the dorsal (DVN; prefrontal, parietal nodes) or ventral (VVN; frontal-temporal, fusiform nodes) matures first, thus leading the neuro-cognitive developmental trajectory. Three age-dependent measures are reported: (i) the CTh at network nodes; (ii) the matrix of intra-network structural connectivity (edges); and (iii) the proficiency in network-related neuropsychological tests. Typically developing children (age ~6 years), adolescents (~11 years), and adults (~21 years) were tested using multiple-acquisition structural T1-weighted magnetic resonance imaging (MRI) and neuropsychology. MRI images reconstructed into a gray/white/pial matter boundary model were used for CTh evaluation. No significant group differences in CTh and in the matrix of edges were found for DVN (except for the left prefrontal), but a significantly thicker cortex in children for VVN with reduced prefrontal ventral-fusiform connectivity and with an abundance of connections in adolescents. The higher performance in children on tests related to DVN corroborates the age-dependent MRI structural connectivity findings. The current findings are consistent with an earlier maturational course of DVN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhz053DOI Listing
December 2019

Somatotopically specific primary somatosensory connectivity to salience and default mode networks encodes clinical pain.

Pain 2019 07;160(7):1594-1605

Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.

Although several studies have found that chronic pain is characterized by increased cross-network connectivity between salience network, sensorimotor network, and default mode network (DMN), a large sample-size investigation allowing for a more reliable evaluation of somatotopic specificity and subgroup analyses with linkage to clinical pain intensity has been lacking. We enrolled healthy adults and a large cohort of patients (N = 181) suffering from chronic low back pain (cLBP). To specifically link brain connectivity with clinical pain intensity, patients were scanned at baseline and after performing physical maneuvers that exacerbated pain. Compared with healthy adults, patients with cLBP demonstrated increased connectivity between the functionally localized back representation in the primary somatosensory cortex (S1back) and both salience network and DMN. Pain exacerbation maneuvers increased S1back connectivity to salience network regions, but decreased connectivity to DMN, with greater pain intensity increase associated with greater shifts in these connectivity patterns. Furthermore, only in patients with cLBP reporting high pain catastrophizing, DMN connectivity was increased to a cardinal node of the salience network, anterior insula cortex, which was correlated with increased postmaneuver pain in this cLBP subgroup. Hence, increased information transfer between salience processing regions, particularly anterior insula, and DMN may be strongly influenced by pain catastrophizing. Increased information transfer between the salience network and S1 likely plays an important role in shifting nociceptive afference away from self-referential processing, reallocating attentional focus, and affective coding of nociceptive afference from specific body areas. These results demonstrate S1 somatotopic specificity for cross-network connectivity in encoding clinical back pain and moderating influence of catastrophizing for DMN/insula connectivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.pain.0000000000001541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586503PMC
July 2019

Age-related alterations in axonal microstructure in the corpus callosum measured by high-gradient diffusion MRI.

Neuroimage 2019 05 18;191:325-336. Epub 2019 Feb 18.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.

Cerebral white matter exhibits age-related degenerative changes during the course of normal aging, including decreases in axon density and alterations in axonal structure. Noninvasive approaches to measure these microstructural alterations throughout the lifespan would be invaluable for understanding the substrate and regional variability of age-related white matter degeneration. Recent advances in diffusion magnetic resonance imaging (MRI) have leveraged high gradient strengths to increase sensitivity toward axonal size and density in the living human brain. Here, we examined the relationship between age and indices of axon diameter and packing density using high-gradient strength diffusion MRI in 36 healthy adults (aged 22-72) in well-defined central white matter tracts in the brain. A recently validated method for inferring the effective axonal compartment size and packing density from diffusion MRI measurements acquired with 300 mT/m maximum gradient strength was applied to the in vivo human brain to obtain indices of axon diameter and density in the corpus callosum, its sub-regions, and adjacent anterior and posterior fibers in the forceps minor and forceps major. The relationships between the axonal metrics, corpus callosum area and regional gray matter volume were also explored. Results revealed a significant increase in axon diameter index with advancing age in the whole corpus callosum. Similar analyses in sub-regions of the corpus callosum showed that age-related alterations in axon diameter index and axon density were most pronounced in the genu of the corpus callosum and relatively absent in the splenium, in keeping with findings from previous histological studies. The significance of these correlations was mirrored in the forceps minor and forceps major, consistent with previously reported decreases in FA in the forceps minor but not in the forceps major with age. Alterations in the axonal imaging metrics paralleled decreases in corpus callosum area and regional gray matter volume with age. Among older adults, results from cognitive testing suggested an association between larger effective compartment size in the corpus callosum, particularly within the genu of the corpus callosum, and lower scores on the Montreal Cognitive Assessment, largely driven by deficits in short-term memory. The current study suggests that high-gradient diffusion MRI may be sensitive to the axonal substrate of age-related white matter degeneration reflected in traditional DTI metrics and provides further evidence for regionally selective alterations in white matter microstructure with advancing age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2019.02.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467051PMC
May 2019

Machine learning-based prediction of clinical pain using multimodal neuroimaging and autonomic metrics.

Pain 2019 Mar;160(3):550-560

Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.

Although self-report pain ratings are the gold standard in clinical pain assessment, they are inherently subjective in nature and significantly influenced by multidimensional contextual variables. Although objective biomarkers for pain could substantially aid pain diagnosis and development of novel therapies, reliable markers for clinical pain have been elusive. In this study, individualized physical maneuvers were used to exacerbate clinical pain in patients with chronic low back pain (N = 53), thereby experimentally producing lower and higher pain states. Multivariate machine-learning models were then built from brain imaging (resting-state blood-oxygenation-level-dependent and arterial spin labeling functional imaging) and autonomic activity (heart rate variability) features to predict within-patient clinical pain intensity states (ie, lower vs higher pain) and were then applied to predict between-patient clinical pain ratings with independent training and testing data sets. Within-patient classification between lower and higher clinical pain intensity states showed best performance (accuracy = 92.45%, area under the curve = 0.97) when all 3 multimodal parameters were combined. Between-patient prediction of clinical pain intensity using independent training and testing data sets also demonstrated significant prediction across pain ratings using the combined model (Pearson's r = 0.63). Classification of increased pain was weighted by elevated cerebral blood flow in the thalamus, and prefrontal and posterior cingulate cortices, and increased primary somatosensory connectivity to frontoinsular cortex. Our machine-learning approach introduces a model with putative biomarkers for clinical pain and multiple clinical applications alongside self-report, from pain assessment in noncommunicative patients to identification of objective pain endophenotypes that can be used in future longitudinal research aimed at discovery of new approaches to combat chronic pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.pain.0000000000001417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377310PMC
March 2019

Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI.

Sci Rep 2018 11 20;8(1):17062. Epub 2018 Nov 20.

Stephen E. and Catherine Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.

Functional MRI may identify critical windows of opportunity for drug delivery and distinguish between early treatment responders and non-responders. Using diffusion-weighted, dynamic contrast-enhanced, and dynamic susceptibility contrast MRI, as well as pro-angiogenic and pro-inflammatory blood markers, we prospectively studied the physiologic tumor-related changes in fourteen newly diagnosed glioblastoma patients during standard therapy. 153 MRI scans and blood collection were performed before chemoradiation (baseline), weekly during chemoradiation (week 1-6), monthly before each cycle of adjuvant temozolomide (pre-C1-C6), and after cycle 6. The apparent diffusion coefficient, volume transfer coefficient (K), and relative cerebral blood volume (rCBV) and flow (rCBF) were calculated within the tumor and edema regions and compared to baseline. Cox regression analysis was used to assess the effect of clinical variables, imaging, and blood markers on progression-free (PFS) and overall survival (OS). After controlling for additional covariates, high baseline rCBV and rCBF within the edema region were associated with worse PFS (microvessel rCBF: HR = 7.849, p = 0.044; panvessel rCBV: HR = 3.763, p = 0.032; panvessel rCBF: HR = 3.984; p = 0.049). The same applied to high week 5 and pre-C1 K within the tumor region (week 5 K: HR = 1.038, p = 0.003; pre-C1 K: HR = 1.029, p = 0.004). Elevated week 6 VEGF levels were associated with worse OS (HR = 1.034; p = 0.004). Our findings suggest a role for rCBV and rCBF at baseline and K and VEGF levels during treatment as markers of response. Functional imaging changes can differ substantially between tumor and edema regions, highlighting the variable biologic and vascular state of tumor microenvironment during therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-34820-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244161PMC
November 2018

Development of Prefrontal Cortical Connectivity and the Enduring Effect of Learned Value on Cognitive Control.

J Cogn Neurosci 2019 01 29;31(1):64-77. Epub 2018 Aug 29.

Harvard University.

Inhibitory control, the capacity to suppress an inappropriate response, is a process employed for guiding action selection in the service of goal-directed behavior. Under neutral circumstances, inhibitory control success improves from childhood to adulthood and has been associated with developmental shifts in functional activation and connectivity of the PFC. However, the ability to exercise inhibitory control is challenged in certain contexts by including appetitive cues, a phenomenon that may be particularly pronounced in youths. Here, we examine the magnitude and temporal persistence of learned value's influence on inhibitory control in a cross-sectional sample of 8- to 25-year-olds. Participants first underwent conditioning of a motor approach response to two initially neutral cues, with one cue reinforced with monetary reward and the other with no monetary outcome. Subsequently, during fMRI, participants reencountered these cues as no-go targets in a nonreinforced go/no-go paradigm. Although the influence of learned value increasingly disrupted inhibitory control with increasing age, in young adults this pattern remitted over the course of the task, whereas during adolescence the impairing effect of reward history persisted. Successful no-go performance to the previously rewarded target was related to greater recruitment of the right inferior frontal gyrus and age-related increase in functional connectivity between the inferior frontal gyrus and the ventromedial PFC for the previously rewarded no-go target over the control target. Together, results indicate the complex influence of value on goals over development relies upon the increased coordination of distinct higher-order regions in the PFC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1162/jocn_a_01331DOI Listing
January 2019

Comparison of the clinical performance of upper abdominal PET/DCE-MRI with and without concurrent respiratory motion correction (MoCo).

Eur J Nucl Med Mol Imaging 2018 11 11;45(12):2147-2154. Epub 2018 Jul 11.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th St., Charlestown, MA, 02129, USA.

Purpose: To compare the clinical performance of upper abdominal PET/DCE-MRI with and without concurrent respiratory motion correction (MoCo).

Methods: MoCo PET/DCE-MRI of the upper abdomen was acquired in 44 consecutive oncologic patients and compared with non-MoCo PET/MRI. SUVmax and MTV of FDG-avid upper abdominal malignant lesions were assessed on MoCo and non-MoCo PET images. Image quality was compared between MoCo DCE-MRI and non-MoCo CE-MRI, and between fused MoCo PET/MRI and fused non-MoCo PET/MRI images.

Results: MoCo PET resulted in higher SUVmax (10.8 ± 5.45) than non-MoCo PET (9.62 ± 5.42) and lower MTV (35.55 ± 141.95 cm) than non-MoCo PET (38.11 ± 198.14 cm; p < 0.005 for both). The quality of MoCo DCE-MRI images (4.73 ± 0.5) was higher than that of non-MoCo CE-MRI images (4.53±0.71; p = 0.037). The quality of fused MoCo-PET/MRI images (4.96 ± 0.16) was higher than that of fused non-MoCo PET/MRI images (4.39 ± 0.66; p < 0.005).

Conclusion: MoCo PET/MRI provided qualitatively better images than non-MoCo PET/MRI, and upper abdominal malignant lesions demonstrated higher SUVmax and lower MTV on MoCo PET/MRI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-018-4084-2DOI Listing
November 2018

Stimulus-dependent hemodynamic response timing across the human subcortical-cortical visual pathway identified through high spatiotemporal resolution 7T fMRI.

Neuroimage 2018 11 20;181:279-291. Epub 2018 Jun 20.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA.

Recent developments in fMRI acquisition techniques now enable fast sampling with whole-brain coverage, suggesting fMRI can be used to track changes in neural activity at increasingly rapid timescales. When images are acquired at fast rates, the limiting factor for fMRI temporal resolution is the speed of the hemodynamic response. Given that HRFs may vary substantially in subcortical structures, characterizing the speed of subcortical hemodynamic responses, and how the hemodynamic response shape changes with stimulus duration (i.e. the hemodynamic nonlinearity), is needed for designing and interpreting fast fMRI studies of these regions. We studied the temporal properties and nonlinearities of the hemodynamic response function (HRF) across the human subcortical visual system, imaging superior colliculus (SC), lateral geniculate nucleus of the thalamus (LGN) and primary visual cortex (V1) with high spatiotemporal resolution 7 Tesla fMRI. By presenting stimuli of varying durations, we mapped the timing and nonlinearity of hemodynamic responses in these structures at high spatiotemporal resolution. We found that the hemodynamic response is consistently faster and narrower in subcortical structures than in cortex. However, the nonlinearity in LGN is similar to that in cortex, with shorter duration stimuli eliciting larger and faster responses than would have been predicted by a linear model. Using oscillatory visual stimuli, we tested the frequency response in LGN and found that its BOLD response tracked high-frequency (0.5 Hz) oscillations. The LGN response magnitudes were comparable to V1, allowing oscillatory BOLD signals to be detected in LGN despite the small size of this structure. These results suggest that the increase in the speed and amplitude of the hemodynamic response when neural activity is brief may be the key physiological driver of fast fMRI signals, enabling detection of high-frequency oscillations with fMRI. We conclude that subcortical visual structures exhibit fast and nonlinear hemodynamic responses, and that these dynamics enable detection of fast BOLD signals even within small deep brain structures when imaging is performed at ultra-high field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2018.06.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245599PMC
November 2018

Pharmacodynamics of mutant-IDH1 inhibitors in glioma patients probed by in vivo 3D MRS imaging of 2-hydroxyglutarate.

Nat Commun 2018 04 16;9(1):1474. Epub 2018 Apr 16.

Department of Neurology, Massachusetts General Hospital, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Division of Hematology/Oncology, Harvard Medical School, Boston, MA, 02114, USA.

Inhibitors of the mutant isocitrate dehydrogenase 1 (IDH1) entered recently in clinical trials for glioma treatment. Mutant IDH1 produces high levels of 2-hydroxyglurate (2HG), thought to initiate oncogenesis through epigenetic modifications of gene expression. In this study, we show the initial evidence of the pharmacodynamics of a new mutant IDH1 inhibitor in glioma patients, using non-invasive 3D MR spectroscopic imaging of 2HG. Our results from a Phase 1 clinical trial indicate a rapid decrease of 2HG levels by 70% (CI 13%, P = 0.019) after 1 week of treatment. Importantly, inhibition of mutant IDH1 may lead to the reprogramming of tumor metabolism, suggested by simultaneous changes in glutathione, glutamine, glutamate, and lactate. An inverse correlation between metabolic changes and diffusion MRI indicates an effect on the tumor-cell density. We demonstrate a feasible radiopharmacodynamics approach to support the rapid clinical translation of rationally designed drugs targeting IDH1/2 mutations for personalized and precision medicine of glioma patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-03905-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902553PMC
April 2018