Roberto Maass-Moreno

Real-time FDG PET Guidance during Biopsies and Radiofrequency Ablation Using Multimodality Fusion with Electromagnetic Navigation

PURPOSE To assess the feasibility of combined electromagnetic device tracking and computed tomography (CT)/ultrasonography (US)/fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) fusion for real-time feedback during percutaneous and intraoperative biopsies and hepatic radiofrequency (RF) ablation. MATERIALS AND METHODS In this HIPAA-compliant, institutional review board-approved prospective study with written informed consent, 25 patients (17 men, eight women) underwent 33 percutaneous and three intraoperative biopsies of 36 FDG-avid targets between November 2007 and August 2010. One patient underwent biopsy and RF ablation of an FDG-avid hepatic focus. Targets demonstrated heterogeneous FDG uptake or were not well seen or were totally inapparent at conventional imaging. Preprocedural FDG PET scans were rigidly registered through a semiautomatic method to intraprocedural CT scans. Coaxial biopsy needle introducer tips and RF ablation electrode guider needle tips containing electromagnetic sensor coils were spatially tracked through an electromagnetic field generator. Real-time US scans were registered through a fiducial-based method, allowing US scans to be fused with intraprocedural CT and preacquired FDG PET scans. A visual display of US/CT image fusion with overlaid coregistered FDG PET targets was used for guidance; navigation software enabled real-time biopsy needle and needle electrode navigation and feedback. RESULTS Successful fusion of real-time US to coregistered CT and FDG PET scans was achieved in all patients. Thirty-one of 36 biopsies were diagnostic (malignancy in 18 cases, benign processes in 13 cases). RF ablation resulted in resolution of targeted FDG avidity, with no local treatment failure during short follow-up (56 days). CONCLUSION Combined electromagnetic device tracking and image fusion with real-time feedback may facilitate biopsies and ablations of focal FDG PET abnormalities that would be challenging with conventional image guidance.

Accuracy of 3D volumetric image registration based on CT, MR and PET/CT phantom experiments

Registration is critical for image‐based treatment planning and image‐guided treatment delivery. Although automatic registration is available, manual, visual‐based image fusion using three orthogonal planar views (3P) is always employed clinically to verify and adjust an automatic registration result. However, the 3P fusion can be time consuming, observer dependent, as well as prone to errors, owing to the incomplete 3‐dimensional (3D) volumetric image representations. It is also limited to single‐pixel precision (the screen resolution). The 3D volumetric image registration (3DVIR) technique was developed to overcome these shortcomings. This technique introduces a 4th dimension in the registration criteria beyond the image volume, offering both visual and quantitative correlation of corresponding anatomic landmarks within the two registration images, facilitating a volumetric image alignment, and minimizing potential registration errors. The 3DVIR combines image classification in real‐time to select and visualize a reliable anatomic landmark, rather than using all voxels for alignment. To determine the detection limit of the visual and quantitative 3DVIR criteria, slightly misaligned images were simulated and presented to eight clinical personnel for interpretation. Both of the criteria produce a detection limit of 0.1 mm and 0.1°. To determine the accuracy of the 3DVIR method, three imaging modalities (CT, MR and PET/CT) were used to acquire multiple phantom images with known spatial shifts. Lateral shifts were applied to these phantoms with displacement intervals of 5.0±0.1mm. The accuracy of the 3DVIR technique was determined by comparing the image shifts determined through registration to the physical shifts made experimentally. The registration accuracy, together with precision, was found to be: 0.02±0.09mm for CT/CT images, 0.03±0.07mm for MR/MR images, and 0.03±0.35mm for PET/CT images. This accuracy is consistent with the detection limit, suggesting an absence of detectable systematic error. This 3DVIR technique provides a superior alternative to the 3P fusion method for clinical applications. PACS numbers: 87.57.nj, 87.57.nm, 87.57.‐N, 87.57.‐s

18F-fluorodeoxyglucose Positron Emission Tomography in Kaposi Sarcoma Herpesvirus–Associated Multicentric Castleman Disease: Correlation With Activity, Severity, Inflammatory and Virologic Parameters

BACKGROUND Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (MCD) is a lymphoproliferative inflammatory disorder commonly associated with human immunodeficiency virus (HIV). Its presentation may be difficult to distinguish from HIV and its complications, including lymphoma. Novel imaging strategies could address these problems. METHODS We prospectively characterized (18)F-fluorodeoxyglucose positron emission tomography (PET) findings in 27 patients with KSHV-MCD. Patients were imaged with disease activity and at remission with scans evaluated blind to clinical status. Symptoms, C-reactive protein level, and HIV and KSHV loads were assessed in relation to imaging findings. RESULTS KSHV-MCD activity was associated with hypermetabolic symmetric lymphadenopathy (median maximal standardized uptake value [SUVmax], 6.0; range, 2.0-8.0) and splenomegaly (3.4; 1.2-11.0), with increased metabolism also noted in the marrow (2.1; range, 1.0-3.5) and salivary glands (3.0; range, 2.0-6.0). The (18)F-fluorodeoxyglucose PET abnormalities improved at remission, with significant SUVmax decreases in the lymph nodes (P = .004), spleen (P = .008), marrow (P = .004), and salivary glands (P = .004). Nodal SUVmax correlated with symptom severity (P = .005), C-reactive protein level (R = 0.62; P = .004), and KSHV load (R = 0.54; P = .02) but not HIV load (P = .52). CONCLUSIONS KSHV-MCD activity is associated with (18)F-FDG PET abnormalities of the lymph nodes, spleen, marrow, and salivary glands. These findings have clinical implications for the diagnosis and monitoring of KSHV-MCD and shed light on its pathobiologic mechanism.

Integrated whole-body PET/MRI with 18F-FDG, 18F-FDOPA, and 18F-FDA in paragangliomas in comparison with PET/CT: NIH first clinical experience with a single-injection, dual-modality imaging protocol.

Purpose Paragangliomas (PGLs) are tumors that can metastasize and recur; therefore, lifelong imaging follow-up is required. Hybrid PET/CT is an essential tool to image PGLs. Novel hybrid PET/MRI scanners are currently being studied in clinical oncology. We studied the feasibility of simultaneous whole-body PET/MRI to evaluate patients with PGLs. Methods Fifty-three PGLs or PGL-related lesions from 8 patients were evaluated. All patients underwent a single-injection, dual-modality imaging protocol consisting of a PET/CT and a subsequent PET/MRI scan. Four patients were evaluated with 18F-FDG, 2 with 18F-fluorodihydroxyphenylalanine, and 2 with 18F-fluorodopamine. PET/MRI data were acquired using a hybrid whole-body 3-tesla integrated PET/MRI scanner. PET and MRI data (Dixon sequence for attenuation correction and T2-weighted sequences for anatomic allocation) were acquired simultaneously. Imaging workflow and imaging times were documented. PET/MRI and PET/CT data were visually assessed (blindly) in regards to image quality, lesion detection, and anatomic allocation and delineation of the PET findings. Results With hybrid PET/MRI, we obtained high-quality images in an acceptable acquisition time (median, 31 minutes; range, 25–40 minutes) with good patient compliance. A total of 53 lesions, located in the head and neck area (6 lesions), mediastinum (2 lesions), abdomen and pelvis (13 lesions), lungs (2 lesions), liver (4 lesions), and bones (26 lesions), were evaluated. Fifty-one lesions were detected with PET/MRI and confirmed by PET/CT. Two bone lesions (L4 body, 8 mm, and sacrum, 6 mm) were not detectable on an 18F-FDA scan PET/MRI, likely because 18F-FDA was washed out between PET/CT and PET/MRI acquisitions. Coregistered MRI tended to be superior to coregistered CT for head and neck, abdomen, pelvis, and liver lesions for anatomic allocation and delineation. Conclusions Clinical PGL evaluation with hybrid PET/MRI is feasible with high-quality image and can be obtained in a reasonable time. It could be particularly beneficial for the pediatric population and for precise lesion definition in the head and neck, abdomen, pelvis, and liver.

Prediction of the location and size of the stomach using patient characteristics for retrospective radiation dose estimation following radiotherapy

Following cancer radiotherapy, reconstruction of doses to organs, other than the target organ, is of interest for retrospective health risk studies. Reliable estimation of doses to organs that may be partially within or fully outside the treatment field requires reliable knowledge of the location and size of the organs, e.g., the stomach, which is at risk from abdominal irradiation. The stomach location and size are known to be highly variable between individuals, but have been little studied. Moreover, for treatments conducted years ago, medical images of patients are usually not available in medical records to locate the stomach. In light of the poor information available to locate the stomach in historical dose reconstructions, the purpose of this work was to investigate the variability of stomach location and size among adult male patients and to develop prediction models for the stomach location and size using predictor variables generally available in medical records of radiotherapy patients treated in the past. To collect data on stomach size and position, we segmented the contours of the stomach and of the skeleton on contemporary computed tomography (CT) images for 30 male patients in supine position. The location and size of the stomach was found to depend on body mass index (BMI), ponderal index (PI), and age. For example, the anteroposterior dimension of the stomach was found to increase with increasing BMI (≈0.25 cm kg(-1) m(2)) whereas its craniocaudal dimension decreased with increasing PI (≈-3.3 cm kg(-1) m(3)) and its transverse dimension increased with increasing PI (≈2.5 cm kg(-1) m(3)). Using the prediction models, we generated three-dimensional computational stomach models from a deformable hybrid phantom for three patients of different BMI. Based on a typical radiotherapy treatment, we simulated radiotherapy treatments on the predicted stomach models and on the CT images of the corresponding patients. Those dose calculations demonstrated good agreement between predicted and actual stomachs compared with doses derived from a reference model of the body that might be used in the absence of individual CT scan data.

Registering Molecular Imaging Information into Anatomic Images with Improved Spatial Accuracy

To make molecular imaging useful in the clinic, accurate image registration must be done to correlate nano-scale events to macro-scale anatomy. The 3D volumetric image registration technique uses visual and quantitative measures to identify the most homogeneous color distribution on a volumetric anatomical landmark. Four phantom PET/CT images were acquired with 5.0 plusmn 0.1 mm shift interval. The image registration shift was compared with the positioning shift. An accuracy of 0.1deg and 0.1 mm was achieved. Cranial PET/CT images from 39 patients were examined. It was found that the average head motion was 0.5-1deg and 1-3 mm, even with a stringent head holder. This small but significant misalignment is beyond the capability of conventional visual-based fusion methods used clinically. The 100 mum accuracy is a step forward to register molecular activities to anatomy for high precision interventions

Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging: Implications for cardiovascular risk stratification and clinical trials

Introduction 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) uptake in the artery wall correlates with active inflammation. However, in part due to the low spatial resolution of PET, variation in the apparent arterial wall signal may be influenced by variation in blood FDG activity that cannot be fully corrected for using typical normalization strategies. The purpose of this study was to evaluate the ability of the current common methods to normalize for blood activity and to investigate alternative methods for more accurate quantification of vascular inflammation. Materials and methods The relationship between maximum FDG aorta wall activity and mean blood activity was evaluated in 37 prospectively enrolled subjects aged 55 years or more, treated for hyperlipidemia. Target maximum aorta standardized uptake value (SUV) and mean background reference tissue activity (blood, spleen, liver) were recorded. Target-to-background ratios (TBR) and arterial maximum activity minus blood activity were calculated. Multivariable regression was conducted, predicting uptake values based on variation in background reference and target tissue FDG uptake; adjusting for gender, age, lean body mass (LBM), blood glucose, blood pool activity, and glomerular filtration rate (GFR), where appropriate. Results Blood pool activity was positively associated with maximum artery wall SUV (β = 5.61, P<0.0001) as well as mean liver (β = 6.23, P<0.0001) and spleen SUV (β = 5.20, P<0.0001). Artery wall activity divided by blood activity (TBRBlood) or subtraction of blood activity did not remove the statistically significant relationship to blood activity. Blood pool activity was not related to TBRliver and TBRspleen (β = −0.36, P = NS and β = −0.58, P = NS, respectively) Conclusions In otherwise healthy individuals treated for hyperlipidemia, blood FDG activity is associated with artery wall activity. However, variation in blood activity may mask artery wall signal reflective of inflammation, which requires normalization. Blood-based TBR and subtraction do not sufficiently adjust for blood activity. Warranting further investigation, background reference tissues with cellular uptake such as the liver and spleen may better adjust for variation in blood activity to improve assessment of vascular activity.