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1.
J Nucl Med ; 64(3): 466-471, 2023 03.
Article in English | MEDLINE | ID: mdl-36175138

ABSTRACT

Psychedelic compounds such as 3,4-methylenedioxymethamphetamine (MDMA) have attracted increasing interest in recent years because of their therapeutic potential in psychiatric disorders. To understand the acute effects of psychedelic drugs in vivo, blood-oxygenation-level-dependent (BOLD) functional MRI (fMRI) has been widely used. In particular, fMRI studies have suggested that MDMA leads to inhibition of brain activity, challenging previous hypotheses indicating mainly excitatory effects based, among others, on increased metabolism shown by 18F-FDG functional PET (fPET). However, interpretation of hemodynamic changes induced by psychedelics is difficult because of their potent vascular effects. Methods: We aimed to delineate the acute effects of MDMA using simultaneous PET/fMRI in rats. For this purpose, hemodynamic changes measured by BOLD fMRI were related to alterations in glucose utilization and serotonin transporter (SERT) occupancy using 18F-FDG fPET/fMRI and 11C-DASB PET/fMRI. Results: We show that MDMA induces localized increases in glucose metabolism in limbic projection areas involved in emotional processing. The increased glucose metabolism was accompanied by global cerebral and extracerebral hemodynamic decreases. We further demonstrated a strong correlation between SERT occupancies and regional BOLD reductions after acute MDMA administration. Conclusion: Our data indicate that hemodynamic decreases after acute MDMA administration are of a nonneuronal nature and initiate peripherally. Within the brain, MDMA triggers neuronal activation in limbic projection areas, whereas increased serotonin levels induced by SERT blockage cause neurovascular uncoupling through direct vascular effects. Correct understanding of the in vivo mechanism of MDMA not only supports ongoing research but also warrants a reassessment of previous studies on neuronal effects of psychedelics relying on neurovascular coupling and recommends 18F-FDG fPET as a potentially more robust measure for pharmacologic research.


Subject(s)
Hallucinogens , N-Methyl-3,4-methylenedioxyamphetamine , Rats , Animals , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , N-Methyl-3,4-methylenedioxyamphetamine/metabolism , Fluorodeoxyglucose F18/metabolism , Hallucinogens/pharmacology , Hallucinogens/metabolism , Brain/metabolism , Multimodal Imaging , Glucose/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Positron-Emission Tomography/methods , Magnetic Resonance Imaging/methods
2.
Neuroimage ; 243: 118501, 2021 11.
Article in English | MEDLINE | ID: mdl-34428573

ABSTRACT

Although brain research has taken important strides in recent decades, the interaction and coupling of its different physiological levels is still not elucidated. Specifically, the molecular substrates of resting-state functional connectivity (rs-FC) remain poorly understood. The aim of this study was elucidating interactions between dopamine D2 receptors (D2R) and serotonin transporter (SERT) availabilities in the striatum (CPu) and medial prefrontal cortex (mPFC), two of the main dopaminergic and serotonergic projection areas, and the default-mode network. Additionally, we delineated its interaction with two other prominent resting-state networks (RSNs), the salience network (SN) and the sensorimotor network (SMN). To this extent, we performed simultaneous PET/fMRI scans in a total of 59 healthy rats using [11C]raclopride and [11C]DASB, two tracers used to image quantify D2R and SERT respectively. Edge, node and network-level rs-FC metrics were calculated for each subject and potential correlations with binding potentials (BPND) in the CPu and mPFC were evaluated. We found widespread negative associations between CPu D2R availability and all the RSNs investigated, consistent with the postulated role of the indirect basal ganglia pathway. Correlations between D2Rs in the mPFC were weaker and largely restricted to DMN connectivity. Strikingly, medial prefrontal SERT correlated both positively with anterior DMN rs-FC and negatively with rs-FC between and within the SN, SMN and the posterior DMN, underlining the complex role of serotonergic neurotransmission in this region. Here we show direct relationships between rs-FC and molecular properties of the brain as assessed by simultaneous PET/fMRI in healthy rodents. The findings in the present study contribute to the basic understanding of rs-FC by revealing associations between inter-subject variances of rs-FC and receptor and transporter availabilities. Additionally, since current therapeutic strategies typically target neurotransmitter systems with the aim of normalizing brain function, delineating associations between molecular and network-level brain properties is essential and may enhance the understanding of neuropathologies and support future drug development.


Subject(s)
Corpus Striatum/metabolism , Prefrontal Cortex/metabolism , Receptors, Dopamine D2/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Animals , Brain Mapping , Magnetic Resonance Imaging , Male , Nerve Net/metabolism , Positron-Emission Tomography , Rats , Rest
3.
Neuroimage ; 236: 118045, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33848625

ABSTRACT

Functional connectivity (FC) and resting-state network (RSN) analyses using functional magnetic resonance imaging (fMRI) have evolved into a growing field of research and have provided useful biomarkers for the assessment of brain function in neurological disorders. However, the underlying mechanisms of the blood oxygen level-dependant (BOLD) signal are not fully resolved due to its inherent complexity. In contrast, [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) has been shown to provide a more direct measure of local synaptic activity and may have additional value for the readout and interpretation of brain connectivity. We performed an RSN analysis from simultaneously acquired PET/fMRI data on a single-subject level to directly compare fMRI and [18F]FDG-PET-derived networks during the resting state. Simultaneous [18F]FDG-PET/fMRI scans were performed in 30 rats. Pairwise correlation analysis, as well as independent component analysis (ICA), were used to compare the readouts of both methods. We identified three RSNs with a high degree of similarity between PET and fMRI-derived readouts: the default-mode-like network (DMN), the basal ganglia network and the cerebellar-midbrain network. Overall, [18F]FDG connectivity indicated increased integration between different, often distant, brain areas compared to the results indicated by the more segregated fMRI-derived FC. Additionally, several networks exclusive to either modality were observed using ICA. These networks included mainly bilateral cortical networks of a limited spatial extent for fMRI and more spatially widespread networks for [18F]FDG-PET, often involving several subcortical areas. This is the first study using simultaneous PET/fMRI to report RSNs subject-wise from dynamic [18F]FDG tracer delivery and BOLD fluctuations with both independent component analysis (ICA) and pairwise correlation analysis in small animals. Our findings support previous studies, which show a close link between local synaptic glucose consumption and BOLD-fMRI-derived FC. However, several brain regions were exclusively attributed to either [18F]FDG or BOLD-derived networks underlining the complementarity of this hybrid imaging approach, which may contribute to the understanding of brain functional organization and could be of interest for future clinical applications.


Subject(s)
Brain/diagnostic imaging , Brain/physiology , Cerebrovascular Circulation/physiology , Connectome/methods , Magnetic Resonance Imaging/methods , Nerve Net/diagnostic imaging , Nerve Net/physiology , Positron-Emission Tomography/methods , Animals , Fluorodeoxyglucose F18 , Male , Multimodal Imaging , Radiopharmaceuticals , Rats
4.
Neuroimage ; 196: 161-172, 2019 08 01.
Article in English | MEDLINE | ID: mdl-30981858

ABSTRACT

Brain function is characterized by a convolution of various biochemical and physiological processes, raising the interest whether resting-state functional connectivity derived from hemodynamic scales shows underlying metabolic synchronies. Increasing evidence suggests that metabolic connectivity based on glucose consumption associated PET recordings may serve as a marker of cognitive functions and neuropathologies. However, to what extent fMRI-derived resting-state brain connectivity can also be characterized based on dynamic fluctuations of glucose metabolism and how metabolic connectivity is influenced by [18F]FDG pharmacokinetics remains unsolved. Simultaneous PET/MRI measurements were performed in a total of 26 healthy male Lewis rats. Simultaneously to resting-state fMRI scans, one cohort (n = 15) received classical bolus [18F]FDG injections and dynamic PET images were recorded. In a second cohort (n = 11) [18F]FDG was constantly infused over the entire functional PET/MRI scans. Resting-state fMRI and [18F]FDG-PET connectivity was evaluated using a graph-theory based correlation approach and compared on whole-brain level and for a default-mode network-like structure. Further, pharmacokinetic and tracer uptake influences on [18F]FDG-PET connectivity results were investigated based on the different PET protocols. By integrating simultaneous resting-state fMRI and dynamic [18F]FDG-PET measurements in the rat brain, we identified homotopic correlations between both modalities, suggesting an underlying synchrony between hemodynamic processes and glucose consumption. Furthermore, the presence of the prominent resting-state default-mode network-like structure was not only depicted on a functional scale but also from dynamic fluctuations of [18F]FDG. In addition, the present findings demonstrated strong pharmacokinetic and tracer uptake dependencies of [18F]FDG-PET connectivity outcomes. This study highlights the application of dynamic [18F]FDG-PET to study cognitive brain functions and to decode underlying brain networks in the resting-state. Thereby, PET-derived connectivity outcomes indicated strong dependencies on tracer application regimens and subsequent time-varying tracer pharmacokinetics.


Subject(s)
Brain/metabolism , Magnetic Resonance Imaging , Positron-Emission Tomography , Animals , Brain/diagnostic imaging , Brain Mapping/methods , Fluorodeoxyglucose F18 , Glucose/metabolism , Male , Multimodal Imaging/methods , Neural Pathways/diagnostic imaging , Neural Pathways/metabolism , Rats, Inbred Lew
5.
Brain Struct Funct ; 222(8): 3833-3845, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28474183

ABSTRACT

Relationships between spatially remote brain regions in human have typically been estimated by moment-to-moment correlations of blood-oxygen-level dependent signals in resting-state using functional MRI (fMRI). Recently, studies using subject-to-subject covariance of anatomical volumes, cortical thickness, and metabolic activity are becoming increasingly popular. However, question remains on whether these measures reflect the same inter-region connectivity and brain network organizations. In the current study, we systematically analyzed inter-subject volumetric covariance from anatomical MRI images, metabolic covariance from fluorodeoxyglucose positron emission tomography images from 193 healthy subjects, and resting-state moment-to-moment correlations from fMRI images of a subset of 44 subjects. The correlation matrices calculated from the three methods were found to be minimally correlated, with higher correlation in the range of 0.31, as well as limited proportion of overlapping connections. The volumetric network showed the highest global efficiency and lowest mean clustering coefficient, leaning toward random-like network, while the metabolic and resting-state networks conveyed properties more resembling small-world networks. Community structures of the volumetric and metabolic networks did not reflect known functional organizations, which could be observed in resting-state network. The current results suggested that inter-subject volumetric and metabolic covariance do not necessarily reflect the inter-regional relationships and network organizations as resting-state correlations, thus calling for cautions on interpreting results of inter-subject covariance networks.


Subject(s)
Brain/anatomy & histology , Brain/metabolism , Hemodynamics , Aged , Aged, 80 and over , Brain/diagnostic imaging , Brain Mapping , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neural Pathways/anatomy & histology , Neural Pathways/diagnostic imaging , Neural Pathways/metabolism , Positron-Emission Tomography , Reproducibility of Results
6.
Mol Imaging Biol ; 18(2): 249-57, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26276154

ABSTRACT

PURPOSE: Positron emission tomography (PET) and diffusion-weighted MRI (DW-MRI) were used to characterize the treatment effects of the MEK1/2 inhibitor selumetinib (AZD6244), docetaxel, and their combination in HCT116 tumor-bearing mice on the molecular level. PROCEDURES: Mice were treated with vehicle, selumetinib (25 mg/kg), docetaxel (15 mg/kg), or a combination of both drugs for 7 days and imaged at four time points with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) or 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) followed by DW-MRI to calculate the apparent diffusion coefficient (ADC). Data was cross-validated using the Pearson correlation coefficient (PCC) and compared to histology (IHC). RESULTS: Each drug led to tumor growth inhibition but their combination resulted in regression. Separate analysis of PET or ADC could not provide significant differences between groups. Only PCC combined with IHC analysis revealed the highest therapeutic impact for combination therapy. CONCLUSION: Combination treatment of selumetinib/docetaxel was superior to the respective mono-therapies shown by PCC of PET and ADC in conjunction with histology.


Subject(s)
Benzimidazoles/therapeutic use , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/drug therapy , Dideoxynucleosides/metabolism , Diffusion Magnetic Resonance Imaging/methods , Fluorodeoxyglucose F18/metabolism , Positron-Emission Tomography/methods , Taxoids/therapeutic use , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzimidazoles/pharmacology , Cell Proliferation/drug effects , Docetaxel , Drug Synergism , HCT116 Cells , Humans , Immunohistochemistry , Mice , Taxoids/pharmacology , Xenograft Model Antitumor Assays
7.
J Nucl Med ; 56(2): 165-8, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25593114

ABSTRACT

The combination of PET and MR imaging forms a powerful new imaging modality, PET/MR. The major advantages of concurrent PET/MR acquisitions range from patient comfort and increased throughput to multiparametric imaging and are evaluated and reviewed in this paper specifically with respect to their applications in research and diagnostics. Alongside the use of PET/MR in the field of preclinical research, this paper illuminates the impact of this new modality in the clinical field in such areas as neurology, oncology, and cardiology. Now that PET/MR technology has matured, attention is needed on standardizing education for nuclear and radiologic technologists and physicians specifically for this combined modality. Furthermore, the impact of this combined modality on health economy needs to be addressed in more detail to further propel its use.


Subject(s)
Magnetic Resonance Imaging , Multimodal Imaging , Positron-Emission Tomography , Animals , Equipment Design , Humans , Mice , Mice, Nude , Myositis/diagnostic imaging , Myositis/pathology , Semiconductors , Technology, Radiologic
8.
Histol Histopathol ; 30(5): 601-13, 2015 May.
Article in English | MEDLINE | ID: mdl-25504583

ABSTRACT

Especially for neuroscience and the development of new biomarkers, a direct correlation between in vivo imaging and histology is essential. However, this comparison is hampered by deformation and shrinkage of tissue samples caused by fixation, dehydration and paraffin embedding. We used magnetic resonance (MR) imaging and computed tomography (CT) imaging to analyze the degree of shrinkage on murine brains for various fixatives. After in vivo imaging using 7 T MRI, animals were sacrificed and the brains were dissected and immediately placed in different fixatives, respectively: zinc-based fixative, neutral buffered formalin (NBF), paraformaldehyde (PFA), Bouin-Holland fixative and paraformaldehyde-lysine-periodate (PLP). The degree of shrinkage based on mouse brain volumes, radiodensity in Hounsfield units (HU), as well as non-linear deformations were obtained. The highest degree of shrinkage was observed for PLP (68.1%, P < 0.001), followed by PFA (60.2%, P<0.001) and NBF (58.6%, P<0.001). The zinc-based fixative revealed a low shrinkage with only 33.5% (P<0.001). Compared to NBF, the zinc-based fixative shows a slightly higher degree of deformations, but is still more homogenous than PFA. Tissue shrinkage can be monitored non-invasively with CT and MR. Zinc-based fixative causes the smallest degree of brain shrinkage and only small deformations and is therefore recommended for in vivo ex vivo comparison studies.


Subject(s)
Brain/drug effects , Brain/diagnostic imaging , Fixatives/chemistry , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Acetic Acid/chemistry , Animals , Formaldehyde/chemistry , Lysine/chemistry , Mice , Mice, Inbred BALB C , Paraffin Embedding , Periodic Acid/chemistry , Picrates/chemistry , Polymers/chemistry , Time Factors , Tissue Fixation , Zinc/chemistry
9.
Nat Med ; 20(12): 1485-92, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25384087

ABSTRACT

The dynamics of ß-amyloid deposition and related second-order physiological effects, such as regional cerebral blood flow (rCBF), are key factors for a deeper understanding of Alzheimer's disease (AD). We present longitudinal in vivo data on the dynamics of ß-amyloid deposition and the decline of rCBF in two different amyloid precursor protein (APP) transgenic mouse models of AD. Using a multiparametric positron emission tomography and magnetic resonance imaging approach, we demonstrate that in the presence of cerebral ß-amyloid angiopathy (CAA), ß-amyloid deposition is accompanied by a decline of rCBF. Loss of perfusion correlates with the growth of ß-amyloid plaque burden but is not related to the number of CAA-induced microhemorrhages. However, in a mouse model of parenchymal ß-amyloidosis and negligible CAA, rCBF is unchanged. Because synaptically driven spontaneous network activity is similar in both transgenic mouse strains, we conclude that the disease-related decline of rCBF is caused by CAA.


Subject(s)
Amyloid beta-Peptides/metabolism , Brain/pathology , Cerebral Amyloid Angiopathy/pathology , Cerebral Hemorrhage/pathology , Cerebrovascular Circulation , Plaque, Amyloid/pathology , Amyloid beta-Protein Precursor/genetics , Aniline Compounds , Animals , Benzothiazoles , Brain/diagnostic imaging , Brain/metabolism , Cerebral Amyloid Angiopathy/diagnostic imaging , Cerebral Amyloid Angiopathy/metabolism , Cerebral Hemorrhage/diagnostic imaging , Disease Models, Animal , Female , Longitudinal Studies , Magnetic Resonance Imaging , Mice , Mice, Transgenic , Multimodal Imaging , Perfusion Imaging , Plaque, Amyloid/diagnostic imaging , Plaque, Amyloid/metabolism , Positron-Emission Tomography , Radiopharmaceuticals , Thiazoles
10.
Mol Imaging ; 132014.
Article in English | MEDLINE | ID: mdl-25430886

ABSTRACT

We aimed to quantitatively characterize the treatment effects of docetaxel in the HCT116 xenograft mouse model, applying diffusion-weighted magnetic resonance imaging (MRI) and positron emission tomography (PET) using 2-deoxy-2-[¹8F]fluoro-d-glucose ([¹8F]FDG) and 3'-deoxy-3'-[¹8F]-fluorothymidine ([¹8F]FLT). Mice were imaged at four time points over 8 days. Docetaxel (15 mg/kg) was administered after a baseline scan. Voxel-wise scatterplots of PET and apparent diffusion coefficient (ADC) data of tumor volumes were evaluated with a threshold cluster analysis and compared to histology (GLUT1, GLUT3, Ki67, activated caspase 3a). Compared to the extensive tumor growth observed in the vehicle-treated group (from 0.32 ± 0.21 cm³ to 0.69 ± 0.40 cm³), the administration of docetaxel led to tumor growth stasis (from 0.32 ± 0.20 cm³ to 0.45 ± 0.23 cm³). The [¹8F]FDG/ADC cluster analysis and the evaluation of peak histogram values revealed a significant treatment effect matching histology as opposed to [¹8F]FLT/ADC. [¹8F]FLT uptake and the Ki67 index were not in good agreement. Our voxel-based cluster analysis uncovered treatment effects not seen in the separate inspection of PET and MRI data and may be used as an independent analysis tool. [¹8F]FLT/ADC cluster analysis could still point out the treatment effect; however, [¹8F]FDG/ADC reflected the histology findings in higher agreement.


Subject(s)
Antineoplastic Agents/administration & dosage , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Dideoxynucleosides , Radiopharmaceuticals , Taxoids/administration & dosage , Animals , Diffusion Magnetic Resonance Imaging , Docetaxel , Female , Fluorodeoxyglucose F18 , HCT116 Cells , Humans , Mice , Multimodal Imaging , Positron-Emission Tomography , Treatment Outcome , Xenograft Model Antitumor Assays
11.
J Nucl Med ; 55(Supplement 2): 11S-18S, 2014 Jun 01.
Article in English | MEDLINE | ID: mdl-24833493

ABSTRACT

Combined PET and MR imaging (PET/MR imaging) has progressed tremendously in recent years. The focus of current research has shifted from technologic challenges to the application of this new multimodal imaging technology in the areas of oncology, cardiology, neurology, and infectious diseases. This article reviews studies in preclinical and clinical translation. The common theme of these initial results is the complementary nature of combined PET/MR imaging that often provides additional insights into biologic systems that were not clearly feasible with just one modality alone. However, in vivo findings require ex vivo validation. Combined PET/MR imaging also triggers a multitude of new developments in image analysis that are aimed at merging and using multimodal information that ranges from better tumor characterization to analysis of metabolic brain networks. The combination of connectomics information that maps brain networks derived from multiparametric MR data with metabolic information from PET can even lead to the formation of a new research field that we would call cometomics that would map functional and metabolic brain networks. These new methodologic developments also call for more multidisciplinarity in the field of molecular imaging, in which close interaction and training among clinicians and a variety of scientists is needed.

12.
Mol Imaging Biol ; 16(3): 295-310, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24668195

ABSTRACT

This workshop was held a year after the initial positron emission tomography/magnetic resonance (PET/MR) workshop in Tübingen, which was recently reported in this journal. The discussions at the 2013 workshop, however, differed substantially from those of the initial workshop, attesting to the progress of combined PET/MR as an innovative imaging modality. Discussions were focused on the search for truly novel, unique clinical and research applications as well as technical issues such as reliable and accurate approaches for attenuation and scatter correction of PET emission data. The workshop provided hands-on experience with PET and MR imaging. In addition, structured and moderated open discussion sessions, including six dialogue boards and two roundtable discussions, provided input from current and future PET/MR imaging users. This summary provides a snapshot of the current achievements and challenges for PET/MR.


Subject(s)
Magnetic Resonance Imaging , Multimodal Imaging , Positron-Emission Tomography , Humans
13.
Neuroimage ; 89: 271-9, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-24316549

ABSTRACT

The study of brain activation in small animals is of high interest for neurological research. In this study, we proposed a protocol to monitor brain activation in rats following whisker stimulation using the short half-life PET tracer [(15)O]H2O as a marker for cerebral blood flow. This technique enables the study of baseline and activation conditions in fast succession within the same scanning session. Furthermore, we compared the results obtained from PET imaging with additional BOLD-fMRI data acquired in the same animals within the same anesthetic session in immediate succession. Although the maximum relative signal changes during brain activity observed with PET were substantially higher compared to the BOLD-fMRI results, statistical analyses showed that the number of activated voxels in PET was lower compared to the fMRI measurements. Furthermore, there was a difference in the activation centers in both the shape and location between PET and fMRI. The discrepancy in the number of activated voxels could be attributed to a lower overall contrast-to-noise ratio of the PET images compared to BOLD-fMRI, whereas the difference in the spatial location indicates a more fundamental process, involving the different physiological origins of the PET and BOLD-fMRI response. This study clearly demonstrates that [(15)O]H2O-PET activation studies may be performed in small laboratory animals, and shows the complementary nature of studying brain activation using [(15)O]H2O-PET and fMRI.


Subject(s)
Brain Mapping , Brain/blood supply , Magnetic Resonance Imaging , Multimodal Imaging , Positron-Emission Tomography , Animals , Brain/diagnostic imaging , Male , Oxygen Radioisotopes , Rats , Rats, Long-Evans
14.
Nat Med ; 19(9): 1184-9, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23975025

ABSTRACT

Combined positron emission tomography (PET) and magnetic resonance imaging (MRI) is a new tool to study functional processes in the brain. Here we study brain function in response to a barrel-field stimulus simultaneously using PET, which traces changes in glucose metabolism on a slow time scale, and functional MRI (fMRI), which assesses fast vascular and oxygenation changes during activation. We found spatial and quantitative discrepancies between the PET and the fMRI activation data. The functional connectivity of the rat brain was assessed by both modalities: the fMRI approach determined a total of nine known neural networks, whereas the PET method identified seven glucose metabolism-related networks. These results demonstrate the feasibility of combined PET-MRI for the simultaneous study of the brain at activation and rest, revealing comprehensive and complementary information to further decode brain function and brain networks.


Subject(s)
Brain/metabolism , Hemodynamics , Magnetic Resonance Imaging , Nerve Net/metabolism , Positron-Emission Tomography , Animals , Brain/diagnostic imaging , Brain/physiology , Brain Mapping , Glucose/metabolism , Male , Nerve Net/diagnostic imaging , Oxygen/metabolism , Rats , Rats, Inbred Lew
15.
Mol Imaging Biol ; 15(4): 361-71, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23515982

ABSTRACT

We report from the First International Workshop on positron emission tomography/magnetic resonance imaging (PET/MRI) that was organized by the University of Tübingen in March 2012. Approximately 100 imaging experts in MRI, PET and PET/computed tomography (CT), among them early adopters of pre-clinical and clinical PET/MRI technology, gathered from March 19 to 24, 2012 in Tübingen, Germany. The objective of the workshop was to provide a forum for sharing first-hand methodological and clinical know-how and to assess the potential of combined PET/MRI in various applications from pre-clinical research to scientific as well as clinical applications in humans. The workshop was comprised of pro-active sessions including tutorials, specific discussion panels and grand rounds. Pre-selected experts moderated the sessions, and feedback from the subsequent discussions is presented here to a greater readership. Naturally, the summaries provided herein are subjective descriptions of the hopes and challenges of PET/MR imaging as seen by the workshop attendees at a very early point in time of adopting PET/MRI technology and, as such, represent only a snapshot of current approaches.


Subject(s)
Magnetic Resonance Imaging , Multimodal Imaging , Positron-Emission Tomography , Clinical Trials as Topic , Germany , Humans , Internationality , Magnetic Resonance Imaging/standards , Multimodal Imaging/standards , Positron-Emission Tomography/standards , Reference Standards , Translational Research, Biomedical
16.
Cancer Res ; 73(5): 1470-80, 2013 Mar 01.
Article in English | MEDLINE | ID: mdl-23345160

ABSTRACT

The metabolites, transporters, and enzymes involved in choline metabolism are regarded as biomarkers for disease progression in a variety of cancers, but their in vivo detection is not ideal. Both magnetic resonance spectroscopy [MRS using chemical shift imaging (CSI) total choline (tCho)] and C-choline positron emission tomography (PET) can probe this pathway, but they have not been compared side by side. In this study, we used the spontaneous murine astrocytoma model SMA560 injected intracranially into syngeneic VM/Dk mice, analyzing animals at various postimplantation time points using dynamic microPET imaging and CSI MRS. We observed an increase in tumor volume and C-choline uptake between days 5 and 18. Similarly, tCho levels decreased at days 5 to 18. We found a negative correlation between the tCho and PET results in the tumor and a positive correlation between the tCho tumor-to-brain ratio and choline uptake in the tumor. PCR results confirmed expected increases in expression levels for most of the transporters and enzymes. Using MRS quantification, a good agreement was found between CSI and C-choline PET data, whereas a negative correlation occurred when CSI was not referenced. Thus, C-choline PET and MRS methods seemed to be complementary in strengths. While advancing tumor proliferation caused an increasing C-choline uptake, gliosis and inflammation potentially accounted for a high peritumoral tCho signal in CSI, as supported by histology and secondary ion mass spectrometry imaging. Our findings provide definitive evidence of the use of MRS, CSI, and PET for imaging tumors in vivo.


Subject(s)
Brain Neoplasms/diagnostic imaging , Glioma/diagnostic imaging , Magnetic Resonance Spectroscopy/methods , Positron-Emission Tomography/methods , Animals , Brain Neoplasms/pathology , Disease Models, Animal , Female , Glioma/pathology , Male , Mass Spectrometry , Mice
17.
Mol Imaging Biol ; 15(2): 155-65, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22811019

ABSTRACT

PURPOSE: Combined PET/MRI studies receive increasing attention, as their combination allows deeper insight into disease progression. We evaluated a novel 1 T benchtop MRI scanner (1T-MRI) for its use in sequential PET/MRI studies. PROCEDURES: Phantom studies were performed, addressing the attenuation caused by the MRI coils. For in vivo studies, PET/MRI data acquired with the 1T-MRI were compared with data using a conventional small animal high-field MRI (7T-MRI) in combination with the same PET scanner. RESULTS: Phantom and in vivo measurements show that the animal beds have no negative impact on the PET scanner performance compared to the 7T-MRI animal bed. Representative images of various animal studies are shown, indicating a wide field for sequential PET-benchtop MRI applications. CONCLUSION: Phantom and in vivo data indicate that sequential PET/MRI studies with this novel setup are comparable to sequential PET/MRI studies using a 7T-MRI in combination with a dedicated PET scanner.


Subject(s)
Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methods , Whole Body Imaging/methods , Animals , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/pathology , Feasibility Studies , Female , Image Processing, Computer-Assisted , Magnetic Resonance Imaging/instrumentation , Mice , Mice, Inbred BALB C , Mice, Transgenic , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Phantoms, Imaging , Positron-Emission Tomography/instrumentation
18.
Mol Imaging Biol ; 15(2): 186-93, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22752651

ABSTRACT

PURPOSE: Assessing information on tumor progression in the RIP1-Tag2 mouse in vivo is a great challenge because the tumors form spontaneously throughout the pancreas and are difficult to detect with current imaging modalities. In this study, we focused on non-invasive magnetic resonance imaging, providing information on tumor growth. PROCEDURES: Tissue relaxation times were measured over time and were compared between tumors and healthy pancreatic tissue. The effects of age and body temperature on these relaxation times, possibly influencing image contrast and therefore detection capabilities, were evaluated. RESULTS: Tumors appeared hyperintense in T2-weighted images when they exceeded 0.8 mm in diameter, and both relaxation times showed significantly higher values in tumors than in the healthy pancreas. CONCLUSION: Visualization and monitoring of these small tumors in vivo is feasible, even under adverse conditions of permanent gut movement. In the mouse model studied, the relaxation times of tumors differed significantly from healthy pancreatic tissue.


Subject(s)
Magnetic Resonance Imaging/methods , Pancreatic Neoplasms/diagnosis , Animals , Body Temperature , Disease Models, Animal , Disease Progression , Histocytochemistry , Mice , Mice, Inbred C3H , Mice, Transgenic , Pancreatic Neoplasms/chemistry , Pancreatic Neoplasms/pathology , Regression Analysis
19.
Eur Radiol ; 22(8): 1776-88, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22752524

ABSTRACT

OBJECTIVES: Technical performance evaluation of a human brain PET/MRI system. METHODS: The magnetic field compatible positron emission tomography (PET) insert is based on avalanche photodiode (APD) arrays coupled with lutetium oxyorthosilicate (LSO) crystals and slip-fits into a slightly modified clinical 3-T MRI system. The mutual interference between the two imaging techniques was minimised by the careful design of the hardware to maintain the quality of the B (0) and B (1) field homogeneity. RESULTS: The signal-to-noise ratio (SNR) and the homogeneity of the MR images were minimally influenced by the presence of the PET. Measurements according to the Function Biomedical Informatics Research Network (FBIRN) protocol proved the combined system's ability to perform functional MRI (fMRI). The performance of the PET insert was evaluated according to the National Electrical Manufacturers Association (NEMA) standard. The noise equivalent count rate (NEC) peaked at 30.7 × 10(3) counts/s at 7.3 kBq/mL. The point source sensitivity was greater than 7 %. The spatial resolution in the centre field of view was less than 3 mm. Patient data sets clearly revealed a noticeably good PET and MR image quality. CONCLUSION: PET and MRI phantom tests and first patient data exhibit the device's potential for simultaneous multiparametric imaging. KEY POINTS: • Combination of PET and MRI is a new emerging imaging technology. • Evaluated brain PET/MRI enables uncompromised imaging performance. • PET/MRI aims to provide multiparametric imaging allowing acquisition of morphology and metabolism.


Subject(s)
Brain/pathology , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methods , Brain Mapping/methods , Equipment Design , Humans , Image Processing, Computer-Assisted/methods , Lutetium/pharmacology , Magnetic Resonance Imaging/instrumentation , Phantoms, Imaging , Positron-Emission Tomography/instrumentation , Reproducibility of Results , Signal-To-Noise Ratio , Silicates/pharmacology
20.
Magn Reson Med ; 65(1): 269-79, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20806353

ABSTRACT

The combination of positron emission tomography and MR in one system is currently emerging and opens up new domains in the functional examinations of living systems. This article reports on relevant influences of a positron emission tomography insert on MR imaging. The basic conditions of main magnetic field and RF field homogeneity were measured as well as image quality and signal-to-noise ratio when applying the usual MR sequence types including echo-planar techniques. Moreover, the influence of the positron emission tomography insert on the RF noise level and on RF interferences was measured by comparing results achieved with and without the positron emission tomography insert. The temporal stability of EPI imaging with and without the positron emission tomography insert was assessed. Small but significant decreases in the signal-to-noise ratio were revealed when the positron emission tomography insert was present, whereas B(0) and B(1) homogeneity as well as RF noise level were not adversely affected. A higher signal intensity drift was found for EPI imaging studies; however, this can be compensated by post processing. In summary, this study shows that positron emission tomography inserts can be designed for and used within an MR system practically, without substantially affecting the MR image quality.


Subject(s)
Artifacts , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/veterinary , Positron-Emission Tomography/instrumentation , Positron-Emission Tomography/veterinary , Subtraction Technique/instrumentation , Subtraction Technique/veterinary , Animals , Equipment Design , Equipment Failure Analysis , Mice , Rats
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