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Ciprian Catana

Harvard University, Martinos Center for Biomedical Imaging, Faculty Member

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Daniela Danková

Katarina Nikolic

SUNY: Stony Brook University

KU Leuven

Lauralee Sylvain

Annika Åstrand

AstraZeneca

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Papers by Ciprian Catana

Epigenetic Signatures of Human Myocardium and Brown Adipose Tissue Revealed with Simultaneous Positron Emission Tomography and Magnetic Resonance of Class I Histone Deacetylases

RationaleHistone deacetylases (HDACs) play a central role in cardiac hypertrophy and fibrosis in ... more RationaleHistone deacetylases (HDACs) play a central role in cardiac hypertrophy and fibrosis in preclinical models. However, their impact in the human heart remains unknown.ObjectiveWe aimed to image HDAC expression in the human heart in vivo with PET-MR (positron emission tomography and magnetic resonance) using [11C]Martinostat, a novel radiotracer targeted to class I HDACs. We further aimed to compare HDAC expression in the heart with its expression in skeletal muscle and brown/white adipose tissue (BAT/WAT).Methods and ResultsThe specificity and selectivity of [11C]Martinostat binding in the heart was assessed in non-human primates (n=2) by in vivo blocking studies and with an ex vivo cellular thermal shift assay (CETSA) of HDAC paralog stabilization by Martinostat. PET-MR imaging of [11C]Martinostat was performed in healthy volunteers (n=6) for 60 minutes to obtain time-activity curves of probe uptake and kinetics. qPCR of class I HDACs was performed in specimens of BAT obtain...

PIDSC Remote Viewing Guidelines Document

Journal of Nuclear Medicine Technology, Dec 30, 2020

Complete the test online no later than March 2024. Your online test will be scored immediately. Y... more Complete the test online no later than March 2024. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 80% of the questions correctly to receive 1.0 CEH (Continuing Education Hour) credit. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test. The current pandemic has created a situation where nuclear medicine practitioners and medical physicists read or process nuclear medicine images remotely from their home office. This article presents recommendations on the components and specifications when setting up a remote viewing station for nuclear medicine imaging.

JCB905433 Supplemental Material1 - Supplemental material for Guidelines for the content and format of PET brain data in publications and archives: A consensus paper

Supplemental material, JCB905433 Supplemental Material1 for Guidelines for the content and format... more Supplemental material, JCB905433 Supplemental Material1 for Guidelines for the content and format of PET brain data in publications and archives: A consensus paper by Gitte M Knudsen, Melanie Ganz, Stefan Appelhoff, Ronald Boellaard, Guy Bormans, Richard E Carson, Ciprian Catana, Doris Doudet, Antony D Gee, Douglas N Greve, Roger N Gunn, Christer Halldin, Peter Herscovitch, Henry Huang, Sune H Keller, Adriaan A Lammertsma, Rupert Lanzenberger, Jeih-San Liow, Talakad G Lohith, Mark Lubberink, Chul H Lyoo, J John Mann, Granville J Matheson, Thomas E Nichols, Martin Nørgaard, Todd Ogden, Ramin Parsey, Victor W Pike, Julie Price, Gaia Rizzo, Pedro Rosa-Neto, Martin Schain, Peter JH Scott, Graham Searle, Mark Slifstein, Tetsuya Suhara, Peter S Talbot, Adam Thomas, Mattia Veronese, Dean F Wong, Maqsood Yaqub, Francesca Zanderigo, Sami Zoghbi and Robert B Innis in Journal of Cerebral Blood Flow & Metabolism

NIMG-85. PBR28 Pet-Mri in GBM Patients Treated with Immunotherapy or Suspected Psuedoprogression

Neuro-Oncology, 2017

BACKGROUND: Perfusion-weighted MRI (PWI) and amino acid PET are increasingly used for glioma imag... more BACKGROUND: Perfusion-weighted MRI (PWI) and amino acid PET are increasingly used for glioma imaging before and after initial treatment. While some studies found a good correlation between these two imaging modalities, others demonstrated discrepancies in various glioma groups and found only a limited spatial overlap of regions with the highest amino acid uptake and highest perfusion. In this study, we compared amino acid uptake measured by PET and relative cerebral blood volume (CBV) from PWI in contrast-enhancing and non-enhancing portions of glioblastomas. METHODS: Contrast-enhanced T1, T2/FLAIR images, CBV maps from PWI, and alpha[C-11]-methyl-L-tryptophan (AMT)-PET images were co-registered in 23 patients (mean age: 56 years) with newly-diagnosed (n=10) or recurrent (n=13) glioblastoma. Tumoral amino acid uptake and CBV, expressed as tumor/contralateral normal brain (cortex for AMT, white matter for CBV, respectively) [T/N] ratios, were measured and compared in contrast-enhancing and non-enhancing (but T2/FLAIR-positive) regions. RESULTS: High AMT uptake on PET was measured in 23 contrast-enhancing regions of 21 patients (mean T/N ratio: 2.43). Similarly, high AMT uptake was also found in 18 adjacent non-enhancing regions of 16 patients (mean T/N: 2.35), indicating tumor-infiltrated brain. On the other hand, 27 contrast-enhancing regions (in 21 patients) showed significantly lower AMT uptake (mean T/N: 1.45; p<0.001). Relative CBV values showed very similar values in high-AMT and low-AMT contrast-enhancing tumor portions (mean T/N white matter ratios: 5.7 in both regions) and were slightly lower in non-enhancing PET+ brain regions (T/N: 4.9). Corresponding AMT and CBV T/N ratios showed no significant correlations. AMT/CBV comparative findings were similar in pre-and post-treatment glioblastoma subgroups. CONCLUSIONS: Amino acid PET and perfusion MRI provide substantially different diagnostic information in newly-diagnosed and recurrent glioblastomas. High amino acid uptake on PET can detect metabolically active tumor portions in contrast-enhancing and non-enhancing regions regardless of perfusion status.

Integrated PET and MRI of the heart

Combined PET/MR Imaging

Combined PET/MR scanners acquire PET and MR data simultaneously, allowing for accurate temporal a... more Combined PET/MR scanners acquire PET and MR data simultaneously, allowing for accurate temporal and spatial matching of PET and MR data. MR has better soft-tissue contrast than CT and can acquire functional data with, for example, diffusionweighted imaging (DWI). In a study that compared PET/CT and PET/MR, PET/CT was found to be superior in detecting lung nodules, but PET/MR revealed additional findings not seen on PET/CT in 55/134 (41%) oncology patients. Radiation dose from PET/MR is substantially less than PET/CT. PET/MR takes longer than PET/CT and is only feasible in patients who can remain still and breath-hold. PET/MR is currently available for patients with selected indications that satisfy enrollment criteria for ongoing clinical research studies.

A Stepping-Stone to Fully Integrated Whole-Body PET/MRI

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2020

PET and MRI have long been used to obtain molecular, functional, and morphologic information to s... more

Integrated [11C]-PBR28 MR-PET imaging in Amyotrophic Lateral Sclerosis (P3.139)

Neurology, 2017

Objective: To characterize glial activation measured by [ 11 C]-PBR28 positron emission tomograph... more Objective: To characterize glial activation measured by [ 11 C]-PBR28 positron emission tomography (PET) in people with amyotrophic lateral sclerosis (ALS). Background: We previously provided preliminary in vivo evidence of increased glial activation in the precentral gyrus in people with ALS. Here, we replicate the initial findings, study longitudinal changes in [ 11 C]-PBR28 uptake, and correlate PET data with MR measures in a large cohort of ALS participants. Design/Methods: Thirty-five people with ALS and 21 healthy controls underwent PBR28 MR-PET. Seven ALS participants had 6-months follow-up scan. Clinical assessments for ALS participants included the upper motor neuron burden scale (UMNB), and ALS functional rating scale (ALSFRS-R). Cortical thinning was measured using Freesurfer, and the difference in [ 11 C]-PBR28 uptake between groups was assessed using voxel-wise analysis. Fractional anisotropy (FA) was estimated using FSL, and correlated with PBR28 uptake in the regions ...

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

European Journal of Nuclear Medicine and Molecular Imaging, 2018

Purpose To compare the clinical performance of upper abdominal PET/DCE-MRI with and without concu... more 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 3) than non-MoCo PET (38.11 ± 198.14 cm 3 ; 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.

Development of Dedicated Brain PET Imaging Devices: Recent Advances and Future Perspectives

Journal of Nuclear Medicine, 2019

Whole-body PET scanners are not optimized for imaging small structures in the human brain. Severa... more Whole-body PET scanners are not optimized for imaging small structures in the human brain. Several PET devices specifically designed for this task have been proposed either for stand-alone operation or as MR-compatible inserts. The main distinctive features of some of the most recent concepts and their performance characteristics, with a focus on spatial resolution and sensitivity, are reviewed. The tradeoffs between the various performance characteristics, desired capabilities, and cost that need to be considered when designing a dedicated brain scanner are presented. Finally, the aspirational goals for future-generation scanners, some of the factors that have contributed to the current status, and how recent advances may affect future developments in dedicated brain PET instrumentation are briefly discussed.

The Dawn of a New Era in Low-Dose PET Imaging

Radiology, 2018

Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation

Brain, behavior, and immunity, Jan 14, 2018

Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoske... more Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [C]--deprenyl-D PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [C]PBR28 PET. 11 FM patients and 11 H...

Measuring temporal stability of positron emission tomography standardized uptake value bias using long-lived sources in a multicenter network

Journal of medical imaging (Bellingham, Wash.), 2018

Positron emission tomography (PET) is a quantitative imaging modality, but the computation of sta... more Positron emission tomography (PET) is a quantitative imaging modality, but the computation of standardized uptake values (SUVs) requires several instruments to be correctly calibrated. Variability in the calibration process may lead to unreliable quantitation. Sealed source kits containing traceable amounts of [Formula: see text] were used to measure signal stability for 19 PET scanners at nine hospitals in the National Cancer Institute's Quantitative Imaging Network. Repeated measurements of the sources were performed on PET scanners and in dose calibrators. The measured scanner and dose calibrator signal biases were used to compute the bias in SUVs at multiple time points for each site over a 14-month period. Estimation of absolute SUV accuracy was confounded by bias from the solid phantoms' physical properties. On average, the intrascanner coefficient of variation for SUV measurements was 3.5%. Over the entire length of the study, single-scanner SUV values varied over a r...

Principles of Simultaneous PET/MR Imaging

Magnetic Resonance Imaging Clinics of North America, 2017

In Vivo Characterization of Inflammation by Combined [ 11 C ]-PBR 28 Pet Imaging and 7 Tesla Mri in Multiple Sclerosis

MRI IN MULTIPLE SCLEROSIS Costanza Gianni', Audrey Fan, Sindhuja Tirumalai Govindarajan, Marc... more MRI IN MULTIPLE SCLEROSIS Costanza Gianni', Audrey Fan, Sindhuja Tirumalai Govindarajan, Marco Loggia, Nicole Zurcher Wimmer, Ciprian Catana, Jacob Hooker, Emanuele Tinelli, Celine Louapre, Thomas A Anderson, R.P. Kinkel, and Caterina Mainero Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, Neurology and Psychiatry, Sapienza, University of Rome, Rome, Italy, Massachusetts General Hospital, Boston, MA, United States, Beth Israel Deaconess Medical Center, Boston, MA, United States

DeepStrain Evidence of Asymptomatic Left Ventricular Diastolic and Systolic Dysfunction in Young Adults With Cardiac Risk Factors

Frontiers in Cardiovascular Medicine

PurposeTo evaluate if a fully-automatic deep learning method for myocardial strain analysis based... more PurposeTo evaluate if a fully-automatic deep learning method for myocardial strain analysis based on magnetic resonance imaging (MRI) cine images can detect asymptomatic dysfunction in young adults with cardiac risk factors.MethodsAn automated workflow termed DeepStrain was implemented using two U-Net models for segmentation and motion tracking. DeepStrain was trained and tested using short-axis cine-MRI images from healthy subjects and patients with cardiac disease. Subsequently, subjects aged 18–45 years were prospectively recruited and classified among age- and gender-matched groups: risk factor group (RFG) 1 including overweight without hypertension or type 2 diabetes; RFG2 including hypertension without type 2 diabetes, regardless of overweight; RFG3 including type 2 diabetes, regardless of overweight or hypertension. Subjects underwent cardiac short-axis cine-MRI image acquisition. Differences in DeepStrain-based left ventricular global circumferential and radial strain and st...

Probabilistic Atlas-Based Generation of Continuous-Valued Attenuation Correction Maps for Hybrid MR-PET Imaging

Introduction To accurately quantify the PET radiotracer concentration, a precise photon attenuati... more Introduction To accurately quantify the PET radiotracer concentration, a precise photon attenuation correction (AC) method is needed to derive voxel-wise linear attenuation coefficient (LAC) maps ("mu-maps") for the imaged subjects. In integrated MR-PET scanners, this has to be accomplished starting from the MR data. We have previously implemented two mu-map generation methods that use dual-echo ultra-short echo time (DUTE) and morphological MR images (MPRAGE) to segment the most relevant classes (i.e. bone, soft tissue, and air cavities) and assign known LACs to each tissue class. [1,2] Though these segmented mu-maps agreed well with the “silver standard” (the mu-maps generated by segmenting the corresponding CT images), it has been shown that considerable bias would still be present in the PET images reconstructed using these maps compared to those obtained using the “gold standard” maps (obtained by scaling the corresponding CT images). [2] Here, we present a novel meth...

Evaluation of Deep Learning–Based Approaches to Segment Bowel Air Pockets and Generate Pelvic Attenuation Maps from CAIPIRINHA-Accelerated Dixon MR Images

Journal of Nuclear Medicine, 2021

Attenuation correction (AC) remains a challenge in pelvis PET/MR imaging. In addition to the segm... more Attenuation correction (AC) remains a challenge in pelvis PET/MR imaging. In addition to the segmentation/model-based approaches, deep learning methods have shown promise in synthesizing accurate pelvis attenuation maps (μ-maps). However, these methods often misclassify air pockets in the digestive tract, which can introduce bias in the reconstructed PET images. The aims of this work were to develop deep learning-based methods to automatically segment air pockets and generate pseudo-CT images from CAIPIRINHA-accelerated MR Dixon images. Methods: A convolutional neural network (CNN) was trained to segment air pockets using 3D CAIPIRINHA-accelerated MR Dixon datasets from 35 subjects and was evaluated against semi-automated segmentations. A separate CNN was trained to synthesize pseudo-CT μ-maps from the Dixon images. Its accuracy was evaluated by comparing the deep learning-, model-and CT-based μ-maps using data from 30 of the subjects. Finally, the impact of different μ-maps and air pocket segmentation methods on the PET quantification was investigated. Results: Air pockets segmented using the CNN agreed well with semi-automated segmentations, with a mean Dice similarity coefficient of 0.75. Volumetric similarity score between two segmentations was 0.85  0.14. The mean absolute relative change (RCs) with respect to the CT-based μ-maps were 2.6% and 5.1% in the whole pelvis for the deep learning and model-based μ-maps, respectively. The average RC between PET images reconstructed with deep learning and CT-based μ-maps was 2.6%. Conclusion: We presented a deep learningbased method to automatically segment air pockets from CAIPIRINHA-accelerated Dixon images with comparable accuracy to semi-automatic segmentations. We also showed that the μ-maps synthesized using a deep learning-based method from CAIPIRINHA-accelerated Dixon images are more accurate than those generated with the model-based approach available on integrated PET/MRI scanner.

A Path to Qualification of PET/MR Scanners for Multicenter Brain Imaging Studies: Evaluation of MR-based Attenuation Correction Methods Using a Patient Phantom

Journal of Nuclear Medicine, 2021

Positron emission tomography and magnetic resonance imaging (PET/MRI) scanners cannot be qualifie... more Positron emission tomography and magnetic resonance imaging (PET/MRI) scanners cannot be qualified in the manner adopted for hybrid PET and computed tomography (CT) devices. The main hurdle with qualification in PET/MRI is that attenuation correction (AC) cannot be adequately measured in conventional PET phantoms due to the difficulty in converting the MRI images of the physical structures (e.g., plastic) into electron density maps. Over the last decade, a plethora of novel MR-based algorithms have been developed to more accurately derive the attenuation properties of the human head, including the skull. Although very promising, none of these techniques has yet emerged as an optimal and universally adopted strategy for AC in PET/MRI. In this work, we propose a path for PET/MRI qualification for multicenter brain imaging studies. Specifically, our solution is to separate the head attenuation correction from the other factors that affect PET data quantification and use a patient as a phantom to assess the former. The emission data collected on the integrated PET/MRI scanner to be qualified should be reconstructed using both MR-and CT-based AC methods and whole-brain qualitative and quantitative (both voxelwise and regional) analyses should be performed. The MR-based approach will be considered satisfactory if the PET quantification bias is within the acceptance criteria specified herein. We have implemented this approach successfully across two PET/MRI scanner manufacturers at two sites.

Neuroimmune signatures in chronic low back pain subtypes

Brain, 2021

We recently showed that patients with different chronic pain conditions (such as chronic low back... more We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct ‘neuroinflammatory signatures’. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not ra...

Epigenetic Signatures of Human Myocardium and Brown Adipose Tissue Revealed with Simultaneous Positron Emission Tomography and Magnetic Resonance of Class I Histone Deacetylases

RationaleHistone deacetylases (HDACs) play a central role in cardiac hypertrophy and fibrosis in ... more RationaleHistone deacetylases (HDACs) play a central role in cardiac hypertrophy and fibrosis in preclinical models. However, their impact in the human heart remains unknown.ObjectiveWe aimed to image HDAC expression in the human heart in vivo with PET-MR (positron emission tomography and magnetic resonance) using [11C]Martinostat, a novel radiotracer targeted to class I HDACs. We further aimed to compare HDAC expression in the heart with its expression in skeletal muscle and brown/white adipose tissue (BAT/WAT).Methods and ResultsThe specificity and selectivity of [11C]Martinostat binding in the heart was assessed in non-human primates (n=2) by in vivo blocking studies and with an ex vivo cellular thermal shift assay (CETSA) of HDAC paralog stabilization by Martinostat. PET-MR imaging of [11C]Martinostat was performed in healthy volunteers (n=6) for 60 minutes to obtain time-activity curves of probe uptake and kinetics. qPCR of class I HDACs was performed in specimens of BAT obtain...

PIDSC Remote Viewing Guidelines Document

Journal of Nuclear Medicine Technology, Dec 30, 2020

Complete the test online no later than March 2024. Your online test will be scored immediately. Y... more Complete the test online no later than March 2024. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 80% of the questions correctly to receive 1.0 CEH (Continuing Education Hour) credit. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test. The current pandemic has created a situation where nuclear medicine practitioners and medical physicists read or process nuclear medicine images remotely from their home office. This article presents recommendations on the components and specifications when setting up a remote viewing station for nuclear medicine imaging.

JCB905433 Supplemental Material1 - Supplemental material for Guidelines for the content and format of PET brain data in publications and archives: A consensus paper

Supplemental material, JCB905433 Supplemental Material1 for Guidelines for the content and format... more Supplemental material, JCB905433 Supplemental Material1 for Guidelines for the content and format of PET brain data in publications and archives: A consensus paper by Gitte M Knudsen, Melanie Ganz, Stefan Appelhoff, Ronald Boellaard, Guy Bormans, Richard E Carson, Ciprian Catana, Doris Doudet, Antony D Gee, Douglas N Greve, Roger N Gunn, Christer Halldin, Peter Herscovitch, Henry Huang, Sune H Keller, Adriaan A Lammertsma, Rupert Lanzenberger, Jeih-San Liow, Talakad G Lohith, Mark Lubberink, Chul H Lyoo, J John Mann, Granville J Matheson, Thomas E Nichols, Martin Nørgaard, Todd Ogden, Ramin Parsey, Victor W Pike, Julie Price, Gaia Rizzo, Pedro Rosa-Neto, Martin Schain, Peter JH Scott, Graham Searle, Mark Slifstein, Tetsuya Suhara, Peter S Talbot, Adam Thomas, Mattia Veronese, Dean F Wong, Maqsood Yaqub, Francesca Zanderigo, Sami Zoghbi and Robert B Innis in Journal of Cerebral Blood Flow & Metabolism

NIMG-85. PBR28 Pet-Mri in GBM Patients Treated with Immunotherapy or Suspected Psuedoprogression

Neuro-Oncology, 2017

BACKGROUND: Perfusion-weighted MRI (PWI) and amino acid PET are increasingly used for glioma imag... more BACKGROUND: Perfusion-weighted MRI (PWI) and amino acid PET are increasingly used for glioma imaging before and after initial treatment. While some studies found a good correlation between these two imaging modalities, others demonstrated discrepancies in various glioma groups and found only a limited spatial overlap of regions with the highest amino acid uptake and highest perfusion. In this study, we compared amino acid uptake measured by PET and relative cerebral blood volume (CBV) from PWI in contrast-enhancing and non-enhancing portions of glioblastomas. METHODS: Contrast-enhanced T1, T2/FLAIR images, CBV maps from PWI, and alpha[C-11]-methyl-L-tryptophan (AMT)-PET images were co-registered in 23 patients (mean age: 56 years) with newly-diagnosed (n=10) or recurrent (n=13) glioblastoma. Tumoral amino acid uptake and CBV, expressed as tumor/contralateral normal brain (cortex for AMT, white matter for CBV, respectively) [T/N] ratios, were measured and compared in contrast-enhancing and non-enhancing (but T2/FLAIR-positive) regions. RESULTS: High AMT uptake on PET was measured in 23 contrast-enhancing regions of 21 patients (mean T/N ratio: 2.43). Similarly, high AMT uptake was also found in 18 adjacent non-enhancing regions of 16 patients (mean T/N: 2.35), indicating tumor-infiltrated brain. On the other hand, 27 contrast-enhancing regions (in 21 patients) showed significantly lower AMT uptake (mean T/N: 1.45; p<0.001). Relative CBV values showed very similar values in high-AMT and low-AMT contrast-enhancing tumor portions (mean T/N white matter ratios: 5.7 in both regions) and were slightly lower in non-enhancing PET+ brain regions (T/N: 4.9). Corresponding AMT and CBV T/N ratios showed no significant correlations. AMT/CBV comparative findings were similar in pre-and post-treatment glioblastoma subgroups. CONCLUSIONS: Amino acid PET and perfusion MRI provide substantially different diagnostic information in newly-diagnosed and recurrent glioblastomas. High amino acid uptake on PET can detect metabolically active tumor portions in contrast-enhancing and non-enhancing regions regardless of perfusion status.

Integrated PET and MRI of the heart

Combined PET/MR Imaging

Combined PET/MR scanners acquire PET and MR data simultaneously, allowing for accurate temporal a... more Combined PET/MR scanners acquire PET and MR data simultaneously, allowing for accurate temporal and spatial matching of PET and MR data. MR has better soft-tissue contrast than CT and can acquire functional data with, for example, diffusionweighted imaging (DWI). In a study that compared PET/CT and PET/MR, PET/CT was found to be superior in detecting lung nodules, but PET/MR revealed additional findings not seen on PET/CT in 55/134 (41%) oncology patients. Radiation dose from PET/MR is substantially less than PET/CT. PET/MR takes longer than PET/CT and is only feasible in patients who can remain still and breath-hold. PET/MR is currently available for patients with selected indications that satisfy enrollment criteria for ongoing clinical research studies.

A Stepping-Stone to Fully Integrated Whole-Body PET/MRI

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2020

PET and MRI have long been used to obtain molecular, functional, and morphologic information to s... more

Integrated [11C]-PBR28 MR-PET imaging in Amyotrophic Lateral Sclerosis (P3.139)

Neurology, 2017

Objective: To characterize glial activation measured by [ 11 C]-PBR28 positron emission tomograph... more Objective: To characterize glial activation measured by [ 11 C]-PBR28 positron emission tomography (PET) in people with amyotrophic lateral sclerosis (ALS). Background: We previously provided preliminary in vivo evidence of increased glial activation in the precentral gyrus in people with ALS. Here, we replicate the initial findings, study longitudinal changes in [ 11 C]-PBR28 uptake, and correlate PET data with MR measures in a large cohort of ALS participants. Design/Methods: Thirty-five people with ALS and 21 healthy controls underwent PBR28 MR-PET. Seven ALS participants had 6-months follow-up scan. Clinical assessments for ALS participants included the upper motor neuron burden scale (UMNB), and ALS functional rating scale (ALSFRS-R). Cortical thinning was measured using Freesurfer, and the difference in [ 11 C]-PBR28 uptake between groups was assessed using voxel-wise analysis. Fractional anisotropy (FA) was estimated using FSL, and correlated with PBR28 uptake in the regions ...

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

European Journal of Nuclear Medicine and Molecular Imaging, 2018

Purpose To compare the clinical performance of upper abdominal PET/DCE-MRI with and without concu... more 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 3) than non-MoCo PET (38.11 ± 198.14 cm 3 ; 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.

Development of Dedicated Brain PET Imaging Devices: Recent Advances and Future Perspectives

Journal of Nuclear Medicine, 2019

Whole-body PET scanners are not optimized for imaging small structures in the human brain. Severa... more Whole-body PET scanners are not optimized for imaging small structures in the human brain. Several PET devices specifically designed for this task have been proposed either for stand-alone operation or as MR-compatible inserts. The main distinctive features of some of the most recent concepts and their performance characteristics, with a focus on spatial resolution and sensitivity, are reviewed. The tradeoffs between the various performance characteristics, desired capabilities, and cost that need to be considered when designing a dedicated brain scanner are presented. Finally, the aspirational goals for future-generation scanners, some of the factors that have contributed to the current status, and how recent advances may affect future developments in dedicated brain PET instrumentation are briefly discussed.

The Dawn of a New Era in Low-Dose PET Imaging

Radiology, 2018

Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation

Brain, behavior, and immunity, Jan 14, 2018

Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoske... more Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [C]--deprenyl-D PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [C]PBR28 PET. 11 FM patients and 11 H...

Measuring temporal stability of positron emission tomography standardized uptake value bias using long-lived sources in a multicenter network

Journal of medical imaging (Bellingham, Wash.), 2018

Positron emission tomography (PET) is a quantitative imaging modality, but the computation of sta... more Positron emission tomography (PET) is a quantitative imaging modality, but the computation of standardized uptake values (SUVs) requires several instruments to be correctly calibrated. Variability in the calibration process may lead to unreliable quantitation. Sealed source kits containing traceable amounts of [Formula: see text] were used to measure signal stability for 19 PET scanners at nine hospitals in the National Cancer Institute's Quantitative Imaging Network. Repeated measurements of the sources were performed on PET scanners and in dose calibrators. The measured scanner and dose calibrator signal biases were used to compute the bias in SUVs at multiple time points for each site over a 14-month period. Estimation of absolute SUV accuracy was confounded by bias from the solid phantoms' physical properties. On average, the intrascanner coefficient of variation for SUV measurements was 3.5%. Over the entire length of the study, single-scanner SUV values varied over a r...

Principles of Simultaneous PET/MR Imaging

Magnetic Resonance Imaging Clinics of North America, 2017

In Vivo Characterization of Inflammation by Combined [ 11 C ]-PBR 28 Pet Imaging and 7 Tesla Mri in Multiple Sclerosis

MRI IN MULTIPLE SCLEROSIS Costanza Gianni', Audrey Fan, Sindhuja Tirumalai Govindarajan, Marc... more MRI IN MULTIPLE SCLEROSIS Costanza Gianni', Audrey Fan, Sindhuja Tirumalai Govindarajan, Marco Loggia, Nicole Zurcher Wimmer, Ciprian Catana, Jacob Hooker, Emanuele Tinelli, Celine Louapre, Thomas A Anderson, R.P. Kinkel, and Caterina Mainero Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, Neurology and Psychiatry, Sapienza, University of Rome, Rome, Italy, Massachusetts General Hospital, Boston, MA, United States, Beth Israel Deaconess Medical Center, Boston, MA, United States

DeepStrain Evidence of Asymptomatic Left Ventricular Diastolic and Systolic Dysfunction in Young Adults With Cardiac Risk Factors

Frontiers in Cardiovascular Medicine

PurposeTo evaluate if a fully-automatic deep learning method for myocardial strain analysis based... more PurposeTo evaluate if a fully-automatic deep learning method for myocardial strain analysis based on magnetic resonance imaging (MRI) cine images can detect asymptomatic dysfunction in young adults with cardiac risk factors.MethodsAn automated workflow termed DeepStrain was implemented using two U-Net models for segmentation and motion tracking. DeepStrain was trained and tested using short-axis cine-MRI images from healthy subjects and patients with cardiac disease. Subsequently, subjects aged 18–45 years were prospectively recruited and classified among age- and gender-matched groups: risk factor group (RFG) 1 including overweight without hypertension or type 2 diabetes; RFG2 including hypertension without type 2 diabetes, regardless of overweight; RFG3 including type 2 diabetes, regardless of overweight or hypertension. Subjects underwent cardiac short-axis cine-MRI image acquisition. Differences in DeepStrain-based left ventricular global circumferential and radial strain and st...

Probabilistic Atlas-Based Generation of Continuous-Valued Attenuation Correction Maps for Hybrid MR-PET Imaging

Introduction To accurately quantify the PET radiotracer concentration, a precise photon attenuati... more Introduction To accurately quantify the PET radiotracer concentration, a precise photon attenuation correction (AC) method is needed to derive voxel-wise linear attenuation coefficient (LAC) maps ("mu-maps") for the imaged subjects. In integrated MR-PET scanners, this has to be accomplished starting from the MR data. We have previously implemented two mu-map generation methods that use dual-echo ultra-short echo time (DUTE) and morphological MR images (MPRAGE) to segment the most relevant classes (i.e. bone, soft tissue, and air cavities) and assign known LACs to each tissue class. [1,2] Though these segmented mu-maps agreed well with the “silver standard” (the mu-maps generated by segmenting the corresponding CT images), it has been shown that considerable bias would still be present in the PET images reconstructed using these maps compared to those obtained using the “gold standard” maps (obtained by scaling the corresponding CT images). [2] Here, we present a novel meth...

Evaluation of Deep Learning–Based Approaches to Segment Bowel Air Pockets and Generate Pelvic Attenuation Maps from CAIPIRINHA-Accelerated Dixon MR Images

Journal of Nuclear Medicine, 2021

Attenuation correction (AC) remains a challenge in pelvis PET/MR imaging. In addition to the segm... more Attenuation correction (AC) remains a challenge in pelvis PET/MR imaging. In addition to the segmentation/model-based approaches, deep learning methods have shown promise in synthesizing accurate pelvis attenuation maps (μ-maps). However, these methods often misclassify air pockets in the digestive tract, which can introduce bias in the reconstructed PET images. The aims of this work were to develop deep learning-based methods to automatically segment air pockets and generate pseudo-CT images from CAIPIRINHA-accelerated MR Dixon images. Methods: A convolutional neural network (CNN) was trained to segment air pockets using 3D CAIPIRINHA-accelerated MR Dixon datasets from 35 subjects and was evaluated against semi-automated segmentations. A separate CNN was trained to synthesize pseudo-CT μ-maps from the Dixon images. Its accuracy was evaluated by comparing the deep learning-, model-and CT-based μ-maps using data from 30 of the subjects. Finally, the impact of different μ-maps and air pocket segmentation methods on the PET quantification was investigated. Results: Air pockets segmented using the CNN agreed well with semi-automated segmentations, with a mean Dice similarity coefficient of 0.75. Volumetric similarity score between two segmentations was 0.85  0.14. The mean absolute relative change (RCs) with respect to the CT-based μ-maps were 2.6% and 5.1% in the whole pelvis for the deep learning and model-based μ-maps, respectively. The average RC between PET images reconstructed with deep learning and CT-based μ-maps was 2.6%. Conclusion: We presented a deep learningbased method to automatically segment air pockets from CAIPIRINHA-accelerated Dixon images with comparable accuracy to semi-automatic segmentations. We also showed that the μ-maps synthesized using a deep learning-based method from CAIPIRINHA-accelerated Dixon images are more accurate than those generated with the model-based approach available on integrated PET/MRI scanner.

A Path to Qualification of PET/MR Scanners for Multicenter Brain Imaging Studies: Evaluation of MR-based Attenuation Correction Methods Using a Patient Phantom

Journal of Nuclear Medicine, 2021

Positron emission tomography and magnetic resonance imaging (PET/MRI) scanners cannot be qualifie... more Positron emission tomography and magnetic resonance imaging (PET/MRI) scanners cannot be qualified in the manner adopted for hybrid PET and computed tomography (CT) devices. The main hurdle with qualification in PET/MRI is that attenuation correction (AC) cannot be adequately measured in conventional PET phantoms due to the difficulty in converting the MRI images of the physical structures (e.g., plastic) into electron density maps. Over the last decade, a plethora of novel MR-based algorithms have been developed to more accurately derive the attenuation properties of the human head, including the skull. Although very promising, none of these techniques has yet emerged as an optimal and universally adopted strategy for AC in PET/MRI. In this work, we propose a path for PET/MRI qualification for multicenter brain imaging studies. Specifically, our solution is to separate the head attenuation correction from the other factors that affect PET data quantification and use a patient as a phantom to assess the former. The emission data collected on the integrated PET/MRI scanner to be qualified should be reconstructed using both MR-and CT-based AC methods and whole-brain qualitative and quantitative (both voxelwise and regional) analyses should be performed. The MR-based approach will be considered satisfactory if the PET quantification bias is within the acceptance criteria specified herein. We have implemented this approach successfully across two PET/MRI scanner manufacturers at two sites.

Neuroimmune signatures in chronic low back pain subtypes

Brain, 2021

We recently showed that patients with different chronic pain conditions (such as chronic low back... more We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct ‘neuroinflammatory signatures’. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not ra...