David K. Shelton

Initial Characterization of a Dedicated Breast PET/CT Scanner During Human Imaging

We have constructed a dedicated breast PET/CT scanner capable of high-resolution functional and anatomic imaging. Here, we present an initial characterization of scanner performance during patient imaging. Methods: The system consisted of a lutetium oxyorthosilicate–based dual–planar head PET camera (crystal size, 3 × 3 × 20 mm) and 768-slice cone-beam CT. The position of the PET heads (separation and height) could be adjusted for varying breast dimensions. For scanning, the patient lay prone on a specialized bed and inserted a single pendent breast through an aperture in the table top. Compression of the breast as used in mammography is not required. PET and CT systems rotate in the coronal plane underneath the patient sequentially to collect fully tomographic datasets. PET images were reconstructed with the fully 3-dimensional maximum a posteriori method, and CT images were reconstructed with the Feldkamp algorithm, then spatially registered and fused for display. Phantom scans were obtained to assess the registration accuracy between PET and CT images and the influence of PET electronics and activity on CT image quality. We imaged 4 women with mammographic findings highly suggestive of breast cancer (breast imaging reporting and data system, category 5) in an ongoing clinical trial. Patients were injected with 18F-FDG and imaged for 12.5 min per breast. From patient data, noise-equivalent counting rates and the singles-to-trues ratio (a surrogate for the randoms fraction) were calculated. Results: The average registration error between PET and CT images was 0.18 mm. PET electronics and activity did not significantly affect CT image quality. For the patient trial, biopsy-confirmed cancers were visualized on dedicated breast PET/CT on all patient scans, including the detection of ductal carcinoma in situ in 1 case. The singles-to-trues ratio was found to be inversely correlated with breast volume in the field of view, suggesting that larger breasts trend toward increased noise-equivalent counting rates for all other things equal. Conclusion: Scanning of the uncompressed breast with dedicated breast PET/CT can accurately visualize suspected lesions in 3 dimensions.

Computed radiography X-ray exposure trends.

RATIONALE AND OBJECTIVES Computed radiography provides correct optical density on film, independent of the incident radiation exposure, but it can result in under- or overexposure of the imaging plate. In the current study, we evaluated the radiation exposure trends of computed radiography over a 2-year period for portable chest examinations to determine and compare the radiographic techniques of the computed radiography system relative to conventional screen-film detectors. METHODS A Fuji computed radiography system was interfaced to a digital workstation to track system usage and examination demographics, including examination type and sensitivity number. Hard-copy films were used for diagnosis. The sensitivity number, a value inversely related to incident exposure on the imaging plate, was used to determine whether the proper techniques were used by the technologists. RESULTS The initial use of the computed radiography system revealed a broad distribution of exposures being used; complaints regarding noisy films (e.g., underexposure) resulted in subsequent overexposure for a significant number of films. A quality-control audit indicating excessive exposure resulted in educational feedback and a tighter distribution of exposures within the optimal range as determined by our radiologists. The average technique was approximately equivalent to a 200-speed system. CONCLUSION Computed radiography provides excellent dynamic range and rescaling capabilities for proper film optical density, and thus fewer repeat examinations. However, underexposure results in suboptimal image quality that is related to excessive quantum mottle. Overexposure requires film audits to limit unnecessary radiation exposure. In general, the optimal exposures are achieved with approximately 1.5-2 times the incident detector exposure of a 400-speed rare-earth system. The ability of computed radiography to reduce radiation exposure is unlikely when compared with a typical rare-earth screen-film combination (400 speed) in terms of adequate image quality for the diagnosis of subtle, low-contrast findings. For certain diagnostic procedures (e.g., nasogastric tube placement verification), lower exposures can be tolerated.

Novel computed tomographic chest metrics to detect pulmonary hypertension

BackgroundEarly diagnosis of pulmonary hypertension (PH) can potentially improve survival and quality of life. Detecting PH using echocardiography is often insensitive in subjects with lung fibrosis or hyperinflation. Right heart catheterization (RHC) for the diagnosis of PH adds risk and expense due to its invasive nature. Pre-defined measurements utilizing computed tomography (CT) of the chest may be an alternative non-invasive method of detecting PH.MethodsThis study retrospectively reviewed 101 acutely hospitalized inpatients with heterogeneous diagnoses, who consecutively underwent CT chest and RHC during the same admission. Two separate teams, each consisting of a radiologist and pulmonologist, blinded to clinical and RHC data, individually reviewed the chest CTs.ResultsMultiple regression analyses controlling for age, sex, ascending aortic diameter, body surface area, thoracic diameter and pulmonary wedge pressure showed that a main pulmonary artery (PA) diameter ≥29 mm (odds ratio (OR) = 4.8), right descending PA diameter ≥19 mm (OR = 7.0), true right descending PA diameter ≥ 16 mm (OR = 4.1), true left descending PA diameter ≥ 21 mm (OR = 15.5), right ventricular (RV) free wall ≥ 6 mm (OR = 30.5), RV wall/left ventricular (LV) wall ratio ≥0.32 (OR = 8.8), RV/LV lumen ratio ≥1.28 (OR = 28.8), main PA/ascending aorta ratio ≥0.84 (OR = 6.0) and main PA/descending aorta ratio ≥ 1.29 (OR = 5.7) were significant predictors of PH in this population of hospitalized patients.ConclusionThis combination of easily measured CT-based metrics may, upon confirmatory studies, aid in the non-invasive detection of PH and hence in the determination of RHC candidacy in acutely hospitalized patients.

High-resolution 18F-FDG PET with MRI for monitoring response to treatment in rheumatoid arthritis

Eur J Nucl Med Mol Imaging (2010) 37:1047 DOI 10.1007/s00259-009-1364-x IMAGE OF THE MONTH High-resolution 18 F-FDG PET with MRI for monitoring response to treatment in rheumatoid arthritis Abhijit J. Chaudhari & Spencer L. Bowen & George W. Burkett & Nathan J. Packard & Felipe Godinez & Anand A. Joshi & Stanley M. Naguwa & David K. Shelton & John C. Hunter & John M. Boone & Michael H. Buonocore & Ramsey D. Badawi Received: 20 November 2009 / Accepted: 10 December 2009 / Published online: 30 January 2010 # The Author(s) 2010. This article is published with open access at Springerlink.com Molecular imaging can potentially provide means for mon- itoring response to therapy in rheumatoid arthritis (RA) early in the course of disease [1].Quantitative measurements of RA disease activity made in the wrist by whole-body PET scanners, however, have inadequate accuracy because of limited spatial resolution [2]. A high-resolution PET/CT scanner for imaging extremities has been built at our insti- tution [3]. In conjunction with a clinical MRI scanner, high- resolution PET/MR images can be obtained for the wrist. The CT image is used for PET/MR image coregistration. A 57-year-old female with established RA was stable until a recent clinical flare-up in the right wrist. Clinical exami- nation revealed synovitis, swelling, and diminished range of motion. The patient also had a history of osteoarthritis (OA). An extremity 18 F-FDG PET/CT scan immediately following MRI at baseline was performed on this patient. Tumor necrosis factor alpha (TNF-α) inhibitor (etanercept) therapy was then initiated as a part of the patient’s standard of care. The patient was re-scanned 5 weeks after starting treatment. The figure shows high-resolution 18 F-FDG PET images (pseudocolor) overlaid on pre-contrast MRI images (gray This work was funded by the NIH grants UL1-RR024146, R01CA129561, R01EB002138 and the UC Davis Imaging Research Center. A. J. Chaudhari (*) : S. L. Bowen : G. W. Burkett : N. J. Packard : F. Godinez : D. K. Shelton : J. C. Hunter : J. M. Boone : M. H. Buonocore : R. D. Badawi Department of Radiology, UC Davis Medical Center, Sacramento, CA, USA e-mail: ajchaudhari@ucdavis.edu A. A. Joshi Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA S. M. Naguwa Department of Internal Medicine, UC Davis Medical Center, Sacramento, CA, USA scale) at baseline (left column) and 5 weeks (right column). Significant reduction in PET signal (suggesting reduced inflammation) in the synovium and at sites of erosions (white arrows) is visible. The green arrow shows inflammation due to OA. Physician examination at 3 months confirmed that this patient responded positively to etanercept. This case illustrates the potential of high-resolution PET with MRI for quantitative visualization of early response to therapy in RA. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. Brenner W. 18F-FDG PET in rheumatoid arthritis: there still is a long way to go. J Nucl Med. 2004;45(6):927–9. 2. Beckers C, Ribbens C, Andre B, Marcelis S, Kaye O, Mathy L, et al. Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET. J Nucl Med. 2004;45(6):956–64. 3. Bowen SL, Wu Y, Chaudhari AJ, Fu L, Packard NJ, Burkett GW, et al. Initial characterization of a dedicated breast PET/CT scanner during human imaging. J Nucl Med. 2009;50(9):1401–8.

Independent Review of Interstitial Lung Disease Associated with Death in TRIBUTE (Paclitaxel and Carboplatin with or without Concurrent Erlotinib) in Advanced Non-small Cell Lung Cancer

Introduction: A rare but serious complication of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is a lung injury syndrome commonly referred to as a drug-induced interstitial lung disease (ILD). It has a typical clinical presentation of rapidly progressive acute or subacute dyspnea and a histopathology of diffuse alveolar damage (DAD). The incidence, severity, and risk factors for EGFR TKI-induced ILD remain poorly understood. Whether concurrent chemotherapy increases its risk is also unclear. The primary focus of this blinded review was to determine the incidence of ILD leading to death in 1059 TRIBUTE patients randomized to chemotherapy plus erlotinib or placebo. Methods: All fatal serious adverse events (SAEs) were reviewed by an independent three-person panel composed of a medical oncologist, radiologist, and pulmonologist not associated with the study and without knowledge of treatment assignment. Fatal respiratory SAEs were identified and assigned to one of four potential attributions: progressive cancer, concurrent illness, drug-induced ILD, or other toxicities not related to ILD. Each panel member first made an independent assignation; then each case was discussed jointly. If needed, consensus was reached by vote. Results: Fatal SAEs were reported in 80 of 1059 patients (7.6%): 53 of 526 patients on erlotinib (10.1%) and 27 of 533 on placebo (5.1%) (p < 0.05). Consensus assignation for 41 fatal respiratory SAEs was as follows: cancer, 18 (44%); concurrent illness, 15 (37%); other toxicities not related to ILD, five (12%); ILD, three (7%). All three ILD cases occurred in the erlotinib arm (3/526; 0.6%). The one biopsy-confirmed case of ILD revealed bronchiolitis obliterans organizing pneumonia, a histopathologic finding that has not previously been reported. All three cases of fatal ILD had a typical clinical presentation of acute or subacute onset of dyspnea with rapid progression to respiratory failure. Conclusions: This independent blinded analysis of the TRIBUTE study identified fatal ILD in 0.6% of cases treated with the combination of erlotinib plus chemotherapy, possibly higher than previous reports of EGFR TKIs alone in the non-Japanese population. Fatal ILD alone does not fully account for the imbalance in fatal SAEs observed in TRIBUTE. EGFR TKI-induced fatal ILD typically presents with acute or subacute dyspnea with rapid progression and a typical histopathology of diffuse alveolar damage both consistent with the acute respiratory distress syndrome, but can also be associated with a histopathology of bronchiolitis obliterans organizing pneumonia. Further studies designed to better understand the underlying pathophysiology and risk factors for ILD are needed.

Iodinated nanoparticles for indirect computed tomography lymphography of the craniocervical and thoracic lymph nodes in normal dogs.

RATIONALE AND OBJECTIVES We evaluated the imaging characteristics of an interstitially or intraperitoneally delivered iodinated particulate contrast agent for computed tomography (CT) lymphography of the craniocervical and thoracic lymph nodes. METHODS We injected 2-4 ml of 15% wt/vol iodinated nanoparticle suspension subcutaneously, submucosally, or intraperitoneally in eight normal dogs. CT and plain radiographic images were obtained prior to contrast administration and 4 hr, 24 hr, and 7 days after injection. Correlation was made to detailed postmortem assessment. RESULTS CT images showed enhancement of regional nodes draining injection sites. Mean attenuation of opacified nodes was 313 +/- 297 (mean +/- standard deviation), 536 +/- 453, and 492 +/- 372 Hounsfield units at 4 hr, 24 hr, and 7 days postinjection, respectively. Lymph node opacification on CT images correlated well with node location found at postmortem. CONCLUSION Craniocervical and thoracic lymph nodes can be effectively opacified from interstitial or intraperitoneal delivery of this iodinated nanoparticulate contrast agent.

Upper extremity radionuclide bone imaging: The wrist and hand

Bone scintigraphy of the hands and wrists represents an important adjunct imaging technique that complements plain film radiographic examination. The use of the three-phase bone scan provides clinical information not only regarding osseous uptake but the blood flow and extravascular distribution of the radiotracer as well. Scintigraphic evaluation of the hands and wrists is employed in acute and chronic conditions. In the event of an equivocal or negative plain film, the bone scan can identify occult fractures. Of particular concern is the identification of scaphoid fractures due to the higher incidence of osteonecrosis. Work related injuries represent a significant health issue. The bone scan can be a part of the algorithm for evaluating chronic pain syndromes including reflex sympathetic dystrophy. The complimentary roles of bone scanning and imaging with gallium-67 citrate or radiolabeled leukocytes has proven useful in the evaluation of acute or chronic osteomyelitis. In addition, the diphosphonates are useful in identifying solitary and multiple primary bone tumors. In the case of primary bone tumor, thallium-201 can be used to evaluate response to therapy. Although uncommon in the hand and wrist, the bone scan can identify metastatic tumors or tumor-related conditions such as hypertrophic osteoarthropathy. Finally, bone scintigraphy may be useful in identifying location and extent in a variety of conditions such as fibrous dysplasia, histiocytosis X, and Pagets disease.

Imaging findings in patients with-right lower quadrant pain: alternative diagnoses to appendicitis.

Patients with right lower quadrant (RLQ) pain referred for imaging studies with a clinical diagnosis of appendicitis may have other pathologic conditions mimicking appendicitis. Appropriate diagnostic imaging may establish other specific diagnoses and thereby play a significant role in determining proper medical or surgical treatment. In this pictorial essay, we present a spectrum of imaging findings in patients whose clinical features were suggestive of appendicitis, but the diagnoses of a broad spectrum of other diseases were established with the imaging studies. The differential diagnoses of diseases mimicking appendicitis are reviewed.

High-resolution 18F-FDG PET/CT for assessing disease activity in rheumatoid and psoriatic arthritis: findings of a prospective pilot study

OBJECTIVE Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) commonly affect the small joints of the wrist and hand. We evaluated the performance of a new, high-resolution extremity positron emission tomography (PET)/CT scanner for characterizing and quantifying pathologies associated with the two arthritides in the wrist and hand joints. METHODS Patients with RA or PsA underwent fluorine-18 fludeoxyglucose ((18)F-FDG) PET/CT wrist and hand imaging, respectively, on the high-resolution scanner. Calibrated CT images and co-registered PET images were reconstructed. PET/CT was derived for the radiocarpal and pisiform-triquetral compartments, joints with erosive changes, sites of synovitis or tenosynovitis and the nail bed and were correlated with clinical and MRI findings. RESULTS Significantly elevated (18)F-FDG uptake was measured for the radiocarpal and pisiform-triquetral compartments and at sites of bone erosion, synovitis, pannus and oedema, compared with unaffected joints (p < 0.05) in patients with RA, consistent with their clinical findings. In patients with PsA, significantly elevated (18)F-FDG uptake was measured for joints with synovitis compared with unaffected joints (p < 0.05), with patterns of (18)F-FDG uptake along the tendons, at the enthesis and in the nail bed, consistent with tenosynovitis, enthesitis and nail dystrophy, respectively. CONCLUSION High-resolution (18)F-FDG PET/CT imaging of the wrist and hand is feasible in an RA or PsA patient cohort and is capable of providing quantifiable measures of disease activity (synovitis, enthesitis, oedema and bone destruction). ADVANCES IN KNOWLEDGE High-resolution PET/CT imaging shows promise as a tool for understanding the pathogenesis of the arthritic process and for non-invasive, objective assessment of RA or PsA severity and therapy selection.

Extensive FDG uptake in accessory muscles of respiration in a patient with shortness of breath.

A 69-year-old man with a history of COPD and small-cell lung cancer was referred for F-18 fluoro-2-deoxy-glucose (FDG) whole-body positron emission tomography (PET) with computed tomography (CT) fusion. The patient had chronic shortness of breath by history, and was noted to have heavy breathing with cough at the time of tracer injection. The PET scan shows marked F-18 FDG uptake in virtually all accessory muscles of inspiration, including the sternocleidomastoids, scalenes, intercostals, diaphragm, crura of diaphragm, and some abdominal wall muscles. In addition, these accessory muscles are noted to be hypertrophied on CT, which likely contributed to the degree of hypermetabolic activity seen on PET.