A Gregory Sorensen

Oslo University Hospital, Kristiania (historical), Oslo County, Norway

Are you A Gregory Sorensen?

Claim your profile

Publications (195)1172.88 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Our understanding of the importance of blood vessels and angiogenesis in cancer has increased considerably over the past decades, and the assessment of tumour vessel calibre and structure has become increasingly important for in vivo monitoring of therapeutic response. The preferred method for in vivo imaging of most solid cancers is MRI, and the concept of vessel-calibre MRI has evolved since its initial inception in the early 1990s. Almost a quarter of a century later, unlike traditional contrast-enhanced MRI techniques, vessel-calibre MRI remains widely inaccessible to the general clinical community. The narrow availability of the technique is, in part, attributable to limited awareness and a lack of imaging standardization. Thus, the role of vessel-calibre MRI in early phase clinical trials remains to be determined. By contrast, regulatory approvals of antiangiogenic agents that are not directly cytotoxic have created an urgent need for clinical trials incorporating advanced imaging analyses, going beyond traditional assessments of tumour volume. To this end, we review the field of vessel-calibre MRI and summarize the emerging evidence supporting the use of this technique to monitor response to anticancer therapy. We also discuss the potential use of this biomarker assessment in clinical imaging trials and highlight relevant avenues for future research.
    Nature Reviews Clinical Oncology 08/2014; Advance Online Publication:1-19. · 15.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chemoradiation (CRT) can significantly modify the radiographic appearance of malignant gliomas, especially within the immediate post-CRT period. Pseudoprogression (PsP) is an increasingly recognized phenomenon in this setting, and is thought to be secondary to increased permeability as a byproduct of the complex process of radiation-induced tissue injury, possibly enhanced by temozolomide. We sought to determine whether the addition of a vascular endothelial growth factor (VEGF) signaling inhibitor (cediranib) to conventional CRT had an impact on the frequency of PsP, by comparing two groups of patients with newly diagnosed glioblastoma before, during, and after CRT.Methods.All patients underwent serial magnetic resonance imaging as part of institutional review board-approved clinical studies. Eleven patients in the control group received only chemoradiation, whereas 29 patients in the study group received chemoradiation and cediranib until disease progression or toxicity. Response assessment was defined according to Response Assessment in Neuro-Oncology criteria, and patients with enlarging lesions were classified into true tumor progressions (TTP) or PsP, based on serial radiographic follow-up.Results.Two patients in the study group (7%) showed signs of apparent early tumor progression, and both were subsequently classified as TTP. Six patients in the control group (54%) showed signs of apparent early tumor progression, and three were subsequently classified as TTP and three as PsP. The frequency of PsP was significantly higher in the control group.Conclusion.Administration of a VEGF inhibitor during and after CRT modifies the expression of PsP by imaging.
    The Oncologist 12/2013; · 4.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The investigation of metabolic pathways disturbed in isocitrate dehydrogenase (IDH) mutant tumors revealed that the hallmark metabolic alteration is the production of D-2-hydroxyglutarate (D-2HG). The biological impact of D-2HG strongly suggests that high levels of this metabolite may play a central role in propagating downstream the effects of mutant IDH, leading to malignant transformation of cells. Hence, D-2HG may be an ideal biomarker for both diagnosing and monitoring treatment response targeting IDH mutations. Magnetic resonance spectroscopy (MRS) is well suited to the task of noninvasive D-2HG detection, and there has been much interest in developing such methods. Here, we review recent efforts to translate methodology using MRS to reliably measure in vivo D-2HG into clinical research.
    The Journal of clinical investigation 09/2013; 123(9):3659-63. · 15.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Measurement of vessel caliber by magnetic resonance imaging (MRI) is a valuable technique for in vivo monitoring of hemodynamic status and vascular development, especially in the brain. Here, we introduce a new paradigm in MRI termed vessel architectural imaging (VAI) that exploits an overlooked temporal shift in the magnetic resonance signal, forming the basis for vessel caliber estimation, and show how this phenomenon can reveal new information on vessel type and function not assessed by any other noninvasive imaging technique. We also show how this biomarker can provide new biological insights into the treatment of patients with cancer. As an example, we demonstrate using VAI that anti-angiogenic therapy can improve microcirculation and oxygen saturation and reduce vessel calibers in patients with recurrent glioblastomas and, more crucially, that patients with these responses have prolonged survival. Thus, VAI has the potential to identify patients who would benefit from therapies.
    Nature medicine 08/2013; · 27.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSEA randomized, phase III, placebo-controlled, partially blinded clinical trial (REGAL [Recentin in Glioblastoma Alone and With Lomustine]) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma. PATIENTS AND METHODS Patients (N = 325) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 2:2:1 to receive (1) cediranib (30 mg) monotherapy; (2) cediranib (20 mg) plus lomustine (110 mg/m(2)); (3) lomustine (110 mg/m(2)) plus a placebo. The primary end point was progression-free survival based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted magnetic resonance imaging (MRI) brain scans.ResultsThe primary end point of progression-free survival (PFS) was not significantly different for either cediranib alone (hazard ratio [HR] = 1.05; 95% CI, 0.74 to 1.50; two-sided P = .90) or cediranib in combination with lomustine (HR = 0.76; 95% CI, 0.53 to 1.08; two-sided P = .16) versus lomustine based on independent or local review of postcontrast T1-weighted MRI. CONCLUSION This study did not meet its primary end point of PFS prolongation with cediranib either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma, although cediranib showed evidence of clinical activity on some secondary end points including time to deterioration in neurologic status and corticosteroid-sparing effects.
    Journal of Clinical Oncology 08/2013; · 18.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background RTOG 0625/ACRIN 6677 is a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma (GBM). This study investigated whether early posttreatment progression on FLAIR or postcontrast MRI assessed by central reading predicts overall survival (OS). Methods Of 123 enrolled patients, 107 had baseline and at least 1 posttreatment MRI. Two central neuroradiologists serially measured bidimensional (2D) and volumetric (3D) enhancement on postcontrast T1-weighted images and volume of FLAIR hyperintensity. Progression status on all posttreatment MRIs was determined using Macdonald and RANO imaging threshold criteria, with a third neuroradiologist adjudicating discrepancies of both progression occurrence and timing. For each MRI pulse sequence, Kaplan-Meier survival estimates and log-rank test were used to compare OS between cases with or without radiologic progression. Results Radiologic progression occurred after 2 chemotherapy cycles (8 weeks) in 9 of 97 (9%), 9 of 73 (12%), and 11 of 98 (11%) 2D-T1, 3D-T1, and FLAIR cases, respectively, and 34 of 80 (43%), 21 of 58 (36%), and 37 of 79 (47%) corresponding cases after 4 cycles (16 weeks). Median OS among patients progressing at 8 or 16 weeks was significantly less than that among nonprogressors, as determined on 2D-T1 (114 vs 278 days and 214 vs 426 days, respectively; P < .0001 for both) and 3D-T1 (117 vs 306 days [P < .0001] and 223 vs 448 days [P = .0003], respectively) but not on FLAIR (201 vs 276 days [P = .38] and 303 vs 321 days [P = .13], respectively). Conclusion Early progression on 2D-T1 and 3D-T1, but not FLAIR MRI, after 8 and 16 weeks of anti-vascular endothelial growth factor therapy has highly significant prognostic value for OS in recurrent GBM.
    Neuro-Oncology 07/2013; 15(7):945-954. · 6.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The prognosis for patients with recurrent glioblastoma remains poor. The purpose of this study was to assess the potential role of MR spectroscopy as an early indicator of response to anti-angiogenic therapy.Methods Thirteen patients with recurrent glioblastoma were enrolled in RTOG 0625/ACRIN 6677, a prospective multicenter trial in which bevacizumab was used in combination with either temozolomide or irinotecan. Patients were scanned prior to treatment and at specific timepoints during the treatment regimen. Postcontrast T1-weighted MRI was used to assess 6-month progression-free survival. Spectra from the enhancing tumor and peritumoral regions were defined on the postcontrast T1-weighted images. Changes in the concentration ratios of n-acetylaspartate/creatine (NAA/Cr), choline-containing compounds (Cho)/Cr, and NAA/Cho were quantified in comparison with pretreatment values.ResultsNAA/Cho levels increased and Cho/Cr levels decreased within enhancing tumor at 2 weeks relative to pretreatment levels (P = .048 and P = .016, respectively), suggesting a possible antitumor effect of bevacizumab with cytotoxic chemotherapy. Nine of the 13 patients were alive and progression free at 6 months. Analysis of receiver operating characteristic curves for NAA/Cho changes in tumor at 8 weeks revealed higher levels in patients progression free at 6 months (area under the curve = 0.85), suggesting that NAA/Cho is associated with treatment response. Similar results were observed for receiver operating characteristic curve analyses against 1-year survival. In addition, decreased Cho/Cr and increased NAA/Cr and NAA/Cho in tumor periphery at 16 weeks posttreatment were associated with both 6-month progression-free survival and 1-year survival.Conclusion Changes in NAA and Cho by MR spectroscopy may potentially be useful as imaging biomarkers in assessing response to anti-angiogenic treatment.
    Neuro-Oncology 05/2013; · 6.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we investigated the structural plasticity of the contralesional motor network in ischemic stroke patients using diffusion magnetic resonance imaging (MRI) and explored a model that combines a MRI-based metric of contralesional network integrity and clinical data to predict functional outcome at 6 months after stroke. MRI and clinical examinations were performed in 12 patients in the acute phase, at 1 and 6 months after stroke. Twelve age- and gender-matched controls underwent 2 MRIs 1 month apart. Structural remodeling after stroke was assessed using diffusion MRI with an automated measurement of generalized fractional anisotropy (GFA), which was calculated along connections between contralesional cortical motor areas. The predictive model of poststroke functional outcome was computed using a linear regression of acute GFA measures and the clinical assessment. GFA changes in the contralesional motor tracts were found in all patients and differed significantly from controls (0.001 ≤ p < 0.05). GFA changes in intrahemispheric and interhemispheric motor tracts correlated with age (p ≤ 0.01); those in intrahemispheric motor tracts correlated strongly with clinical scores and stroke sizes (p ≤ 0.001). GFA measured in the acute phase together with a routine motor score and age were a strong predictor of motor outcome at 6 months (r(2) = 0.96, p = 0.0002). These findings represent a proof of principle that contralesional diffusion MRI measures may provide reliable information for personalized rehabilitation planning after ischemic motor stroke.
    Neurology 06/2012; 79(1):39-46. · 8.25 Impact Factor
  • Tracy T Batchelor, A Gregory Sorensen, David N Louis
    New England Journal of Medicine 05/2012; 366(22):2112-20. · 51.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of the non-injured hemisphere in stroke recovery is poorly understood. In this pilot study, we sought to explore the presence of structural changes detectable by diffusion tensor imaging (DTI) in the contralesional hemispheres of patients who recovered well from ischemic stroke. We analyzed serial DTI data from 16 stroke patients who had moderate initial neurological deficits (NIHSS scores 3-12) and good functional outcome at 3-6 months (NIHSS score 0 or modified Rankin Score ≤1). We segmented the brain tissue in gray and white matter (GM and WM) and measured the apparent diffusion coefficient (ADC) and fractional anisotropy in the infarct, in the contralesional infarct mirror region as well as in concentrically expanding regions around them. We found that GM and WM ADC significantly increased in the infarct region (p < 0.01) from acute to chronic time points, whereas in the infarct mirror region, GM and WM ADC increased (p < 0.01) and WM fractional anisotropy decreased (p < 0.05). No significant changes were detected in other regions. DTI-based metrics are sensitive to regional structural changes in the contralesional hemisphere during stroke recovery. Prospective studies in larger cohorts with varying levels of recovery are needed to confirm our findings.
    European Neurology 05/2012; 67(6):370-6. · 1.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the effects of recent advances in magnetic resonance imaging (MRI) radiofrequency (RF) coil and parallel imaging technology on brain volume measurement consistency. In all, 103 whole-brain MRI volumes were acquired at a clinical 3T MRI, equipped with a 12- and 32-channel head coil, using the T1-weighted protocol as employed in the Alzheimer's Disease Neuroimaging Initiative study with parallel imaging accelerations ranging from 1 to 5. An experienced reader performed qualitative ratings of the images. For quantitative analysis, differences in composite width (CW, a measure of image similarity) and boundary shift integral (BSI, a measure of whole-brain atrophy) were calculated. Intra- and intersession comparisons of CW and BSI measures from scans with equal acceleration demonstrated excellent scan-rescan accuracy, even at the highest acceleration applied. Pairs-of-scans acquired with different accelerations exhibited poor scan-rescan consistency only when differences in the acceleration factor were maximized. A change in the coil hardware between compared scans was found to bias the BSI measure. The most important findings are that the accelerated acquisitions appear to be compatible with the assessment of high-quality quantitative information and that for highest scan-rescan accuracy in serial scans the acquisition protocol should be kept as consistent as possible over time. J. Magn. Reson. Imaging 2012;36:1234-1240. ©2012 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 05/2012; 36(5):1234-40. · 2.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Voxel-based algorithms using acute multiparametric-MRI data have been shown to accurately predict tissue outcome after stroke. We explored the potential of MRI-based predictive algorithms to objectively assess the effects of normobaric oxygen therapy (NBO), an investigational stroke treatment, using data from a pilot study of NBO in acute stroke. The pilot study of NBO enrolled 11 patients randomized to NBO administered for 8 hours, and 8 Control patients who received room-air. Serial MRIs were obtained at admission, during gas therapy, post-therapy, and pre-discharge. Diffusion/perfusion MRI data acquired at admission (pre-therapy) was used in generalized linear models to predict the risk of lesion growth at subsequent time points for both treatment scenarios: NBO or Control. Lesion volume sizes 'during NBO therapy' predicted by Control-models were significantly larger (P = 0.007) than those predicted by NBO models, suggesting that ischemic lesion growth is attenuated during NBO treatment. No significant difference was found between the predicted lesion volumes at later time-points. NBO-treated patients, despite showing larger lesion volumes on Control-models than NBO-models, tended to have reduced lesion growth. This study shows that NBO has therapeutic potential in acute ischemic stroke, and demonstrates the feasibility of using MRI-based algorithms to evaluate novel treatments in early-phase clinical trials.
    Medical gas research. 03/2012; 2(1):5.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mutations in the gene isocitrate dehydrogenase 1 (IDH1) are present in up to 86% of grade II and III gliomas and secondary glioblastoma. Arginine 132 (R132) mutations in the enzyme IDH1 result in excess production of the metabolite 2-hydroxyglutarate (2HG), which could be used as a biomarker for this subset of gliomas. Here, we use optimized in vivo spectral-editing and two-dimensional (2D) correlation magnetic resonance spectroscopy (MRS) methods to unambiguously detect 2HG noninvasively in glioma patients with IDH1 mutations. By comparison, fitting of conventional 1D MR spectra can provide false-positive readouts owing to spectral overlap of 2HG and chemically similar brain metabolites, such as glutamate and glutamine. 2HG was also detected using 2D high-resolution magic angle spinning MRS performed ex vivo on a separate set of glioma biopsy samples. 2HG detection by in vivo or ex vivo MRS enabled detailed molecular characterization of a clinically important subset of human gliomas. This has implications for diagnosis as well as monitoring of treatments targeting mutated IDH1.
    Science translational medicine 01/2012; 4(116):116ra4. · 10.76 Impact Factor
  • Source
    Ovidiu C Andronesi, Borjan A Gagoski, A Gregory Sorensen
    [Show abstract] [Hide abstract]
    ABSTRACT: To improve clinical three-dimensional (3D) MR spectroscopic imaging with more accurate localization and faster acquisition schemes. Institutional review board approval and patient informed consent were obtained. Data were acquired with a 3-T MR imager and a 32-channel head coil in phantoms, five healthy volunteers, and five patients with glioblastoma. Excitation was performed with localized adiabatic spin-echo refocusing (LASER) by using adiabatic gradient-offset independent adiabaticity wideband uniform rate and smooth truncation (GOIA-W[16,4]) pulses with 3.5-msec duration, 20-kHz bandwidth, 0.81-kHz amplitude, and 45-msec echo time. Interleaved constant-density spirals simultaneously encoded one frequency and two spatial dimensions. Conventional phase encoding (PE) (1-cm3 voxels) was performed after LASER excitation and was the reference standard. Spectra acquired with spiral encoding at similar and higher spatial resolution and with shorter imaging time were compared with those acquired with PE. Metabolite levels were fitted with software, and Bland-Altman analysis was performed. Clinical 3D MR spectroscopic images were acquired four times faster with spiral protocols than with the elliptical PE protocol at low spatial resolution (1 cm3). Higher-spatial-resolution images (0.39 cm3) were acquired twice as fast with spiral protocols compared with the low-spatial-resolution elliptical PE protocol. A minimum signal-to-noise ratio (SNR) of 5 was obtained with spiral protocols under these conditions and was considered clinically adequate to reliably distinguish metabolites from noise. The apparent SNR loss was not linear with decreasing voxel sizes because of longer local T2* times. Improvement of spectral line width from 4.8 Hz to 3.5 Hz was observed at high spatial resolution. The Bland-Altman agreement between spiral and PE data is characterized by narrow 95% confidence intervals for their differences (0.12, 0.18 of their means). GOIA-W(16,4) pulses minimize chemical-shift displacement error to 2.1%, reduce nonuniformity of excitation to 5%, and eliminate the need for outer volume suppression. The proposed adiabatic spiral 3D MR spectroscopic imaging sequence can be performed in a standard clinical MR environment. Improvements in image quality and imaging time could enable more routine acquisition of spectroscopic data than is possible with current pulse sequences.
    Radiology 12/2011; 262(2):647-61. · 6.34 Impact Factor
  • Ronald J H Borra, A Gregory Sorensen
    [Show abstract] [Hide abstract]
    ABSTRACT: Concern regarding incidental findings on brain MRI studies has been increasing with the growing use of MRI as tool for scientific investigation. In this article, the authors provide an overview of possible approaches to address incidental findings. Incidental findings are surprisingly common (5%-20% of all examinations), although the percentage of clinically serious abnormalities is low (0.3%-3.4%). At present, there is no consensus concerning the optimal strategy on how to deal with incidental findings, in particular how to fulfill ethical responsibilities appropriately within the constraints of available resources. There are a variety of responses possible, and currently, reasonable guidelines exist for formulating a plan tailored to the needs of each institution that will meet the reasonable expectations of subjects participating in brain research studies.
    Journal of the American College of Radiology: JACR 12/2011; 8(12):848-52.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The abnormal vasculature of the tumor microenvironment supports progression and resistance to treatment. Judicious application of antiangiogenic therapy may normalize the structure and function of the tumor vasculature, promoting improved blood perfusion. However, direct clinical evidence is lacking for improvements in blood perfusion after antiangiogenic therapy. In this study, we used MRI to assess tumor blood perfusion in 30 recurrent glioblastoma patients who were undergoing treatment with cediranib, a pan-VEGF receptor tyrosine kinase inhibitor. Tumor blood perfusion increased durably for more than 1 month in 7 of 30 patients, in whom it was associated with longer survival. Together, our findings offer direct clinical evidence in support of the hypothesis that vascular normalization can increase tumor perfusion and help improve patient survival.
    Cancer Research 11/2011; 72(2):402-7. · 9.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Many patients with stroke are precluded from thrombolysis treatment because the time from onset of their symptoms is unknown. We aimed to test whether a mismatch in visibility of an acute ischaemic lesion between diffusion-weighted MRI (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI (DWI-FLAIR mismatch) can be used to detect patients within the recommended time window for thrombolysis. In this multicentre observational study, we analysed clinical and MRI data from patients presenting between Jan 1, 2001, and May 31, 2009, with acute stroke for whom DWI and FLAIR were done within 12 h of observed symptom onset. Two neurologists masked to clinical data judged the visibility of acute ischaemic lesions on DWI and FLAIR imaging, and DWI-FLAIR mismatch was diagnosed by consensus. We calculated predictive values of DWI-FLAIR mismatch for the identification of patients with symptom onset within 4·5 h and within 6 h and did multivariate regression analysis to identify potential confounding covariates. This study is registered with ClinicalTrials.gov, number NCT01021319. The final analysis included 543 patients. Mean age was 66·0 years (95% CI 64·7-67·3) and median National Institutes of Health Stroke Scale score was 8 (IQR 4-15). Acute ischaemic lesions were identified on DWI in 516 patients (95%) and on FLAIR in 271 patients (50%). Interobserver agreement for acute ischaemic lesion visibility on FLAIR imaging was moderate (κ=0·569, 95% CI 0·504-0·634). DWI-FLAIR mismatch identified patients within 4·5 h of symptom onset with 62% (95% CI 57-67) sensitivity, 78% (72-84) specificity, 83% (79-88) positive predictive value, and 54% (48-60) negative predictive value. Multivariate regression analysis identified a longer time to MRI (p<0·0001), a lower age (p=0·0009), and a larger DWI lesion volume (p=0·0226) as independent predictors of lesion visibility on FLAIR imaging. Patients with an acute ischaemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomised trial of thrombolysis in patients with unknown time of symptom onset. Else Kröner-Fresenius-Stiftung, National Institutes of Health.
    The Lancet Neurology 11/2011; 10(11):978-86. · 23.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A method is presented to correct the effects of motion and motion-related B(0) perturbations on spectroscopic imaging in real time through the use of a volumetric navigator. It is demonstrated that, for an axial slice, lifting the chin significantly disrupts the B(0) homogeneity in the zero-order (frequency), first-order Y (coronal) axis and second-order ZY term. This volumetric navigator is able to measure and correct in real time both head pose and zero- to first-order B(0) inhomogeneities. The volumetric navigator was validated in six volunteers who deliberately lifted and then dropped their chin during the scan. These scans show that motion correction alone is not sufficient to recover the spectral quality. By applying real-time shim adjustments, spectral quality was fully recovered to linewidths below 0.08 ppm and the signal-to-noise ratio to within acceptable limits in five of six subjects. In the sixth subject, 83% of the spectra within the volume of interest were recovered, compared with the worst case nonshim-corrected scan, where none of the voxels fell within these quality bounds. It is shown that the use of a volumetric navigator comes at no additional cost to the scan time or spectral signal-to-noise ratio.
    NMR in Biomedicine 07/2011; 25(2):347-58. · 3.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this work we introduce the concept of correlation chemical shift imaging (CCSI). Novel CCSI pulse sequences are demonstrated on clinical scanners for two-dimensional Correlation Spectroscopy (COSY) and Total Correlation Spectroscopy (TOCSY) imaging experiments. To date there has been limited progress reported towards a feasible and robust multivoxel 2D COSY. Localized 2D TOCSY imaging is shown for the first time in this work. Excitation with adiabatic GOIA-W(16,4) pulses (Gradient Offset Independent Adiabaticity Wurst modulation) provides minimal chemical shift displacement error, reduced lipid contamination from subcutaneous fat, uniform optimal flip angles, and efficient mixing for coupled spins, while enabling short repetition times due to low power requirements. Constant-density spiral readout trajectories are used to acquire simultaneously two spatial dimensions and f(2) frequency dimension in (k(x),k(y),t(2)) space in order to speed up data collection, while f(1) frequency dimension is encoded by consecutive time increments of t(1) in (k(x),k(y),t(1),t(2)) space. The efficient spiral sampling of the k-space enables the acquisition of a single-slice 2D COSY dataset with an 8 × 8 matrix in 8:32  min on 3 T clinical scanners, which makes it feasible for in vivo studies on human subjects. Here we present the first results obtained on phantoms, human volunteers and patients with brain tumors. The patient data obtained by us represent the first clinical demonstration of a feasible and robust multivoxel 2D COSY. Compared to the 2D J-resolved method, 2D COSY and TOCSY provide increased spectral dispersion which scales up with increasing main magnetic field strength and may have improved ability to unambiguously identify overlapping metabolites. It is expected that the new developments presented in this work will facilitate in vivo application of 2D chemical shift correlation MRS in basic science and clinical studies.
    NMR in Biomedicine 07/2011; 25(2):195-209. · 3.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Transverse relaxation time (T(2)) is a basic but very informative MRI parameter, widely used in imaging to examine a host of diseases, including multiple sclerosis, stroke, and tumor. However, short repetition time (TR) is often used to minimize scan time, which may introduce non-negligible errors in T(2) measurement. Specifically, due to the use of refocusing pulse, the steady state magnetization depends not only on TR but also on the TE. Hence, if the TE dependence is not properly accounted for, it may be mistaken as T(2)-induced signal attenuation, leading to non-negligible T(2) underestimation. Our study proposed a fast radio-frequency enforced steady state (FRESS) spin echo (SE) MRI sequence, which saturates the magnetization after the echo and ensures a TE-independent steady state. The proposed FRESS-SE MRI was evaluated with numerical simulation, implemented with echo planar imaging readout, and validated by both phantom and in vivo experiments. In summary, FRESS-SE T(2) MRI technique was developed for fast and accurate T(2) imaging, suitable for in vivo applications.
    NMR in Biomedicine 07/2011; 25(2):189-94. · 3.45 Impact Factor

Publication Stats

10k Citations
1,172.88 Total Impact Points


  • 2013
    • Oslo University Hospital
      Kristiania (historical), Oslo County, Norway
  • 2008–2011
    • Massachusetts Institute of Technology
      • Division of Health Sciences and Technology
      Cambridge, Massachusetts, United States
  • 1996–2011
    • Harvard Medical School
      • • Department of Radiology
      • • Department of Radiation Oncology
      Boston, MA, United States
  • 1991–2011
    • Massachusetts General Hospital
      • • Department of Radiology
      • • Department of Neurology
      • • Martinos Center for Biomedical Imaging
      Boston, MA, United States
  • 2007–2009
    • Max Planck Institute for Neurological Research
      Köln, North Rhine-Westphalia, Germany
  • 2002–2009
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2006–2007
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • Department of Neurology
      Erlangen, Bavaria, Germany
  • 2005
    • University of California, Los Angeles
      • Department of Radiology
      Los Angeles, CA, United States
    • Partners HealthCare
      • Department of Radiology
      Boston, MA, United States
  • 2004
    • Adnan Menderes University
      • Department of Radiology
      Güsel Hissar, Aydın, Turkey
  • 2003
    • University of Münster
      • Department of Clinical Radiology
      Münster, North Rhine-Westphalia, Germany
  • 1999
    • Aarhus University Hospital
      • Department of Neuroradiology
      Aarhus, Central Jutland, Denmark