Standardized uptake values and attenuation correction in 18 F-sodium fluoride PET of the equine foot and fetlock.

Maximal standardized uptake values (SUVmax ) are commonly used for the interpretation of PET studies. Limited information regarding the SUVmax of 18 F-NaF PET in horses is currently available in the literature. The goals of this retrospective secondary analysis study were to provide reference values for 18 F-NaF SUVmax in the equine distal extremity and assess the effect of attenuation correction. Nonattenuation corrected (NAC) and CT-based attenuation corrected (CTAC) SUVmax were obtained from 19 feet and 19 fetlocks. Twenty regions of interest (ROIs) were defined for the foot and 22 for the fetlock. Areas presenting abnormal uptake were excluded. The overall NAC and CTAC SUVmax were 3.6 +/- 1.5 (mean +/- sd) and 5.0 +/- 1.8 for the feet and 2.9 +/- 1.1 and 3.8 +/- 1.4 for the fetlocks, respectively. The 3 ROIs showing the highest attenuation correction were the navicular center (83.4%), navicular flexor surface (74.9%) and distal phalanx flexor surface (81.3%), whereas attenuation correction was only 5.2% at the dorsal aspect of the proximal phalanx. Significant SUVmax differences were observed between the different ROIs (P < 0.0001), with the toe (CTAC SUVmax 7.7 +/- 3.7), dorsal (7.5 +/- 1.9) and central (6.1 +/- 2.2) ROIs of the distal phalanx being significantly higher than those of the other areas. This study demonstrates that attenuation correction affects SUVmax in the equine distal extremity and should be performed if CT data are available. However, as the maximal attenuation correction results in less than doubling the signal intensity, nonattenuation corrected images likely remain relevant for subjective clinical interpretation.

Validation of a dedicated positron emission tomography scanner for imaging of the distal limb of standing horses.

A positron emission tomography (PET) scanner, with an openable ring of detectors, was specifically designed to image the distal limb of standing horses. The goals of this prospective, preclinical, experimental, methods comparison study were to validate the safety of the scanner, assess image quality, and optimize scanning protocols. Six research horses were imaged three times (twice standing, once anesthetized) and six horses in active race training were imaged once under standing sedation. Multiple scans of both front fetlocks were obtained with different scan durations and axial fields of view. A total of 94 fetlock scans were attempted and 90 provided images of diagnostic value. Radiotracer uptake was the main factor affecting image quality, while motion did not represent a major issue. Scan duration and field of view also affected image quality. Eight specific lesions were identified on PET images from anesthetized horses and were all also independently recognized on the PET images obtained on standing horses. Maximal standardized uptake values (SUVmax) had good repeatability for the assessment of specific lesions among different scans. Three feet and six carpi were also successfully imaged. This study validated the safety and practicality of a PET scanner specifically designed to image the distal limb in standing horses. Proper preparation of horses, similar to bone scintigraphy, is important for image quality. A 4-min scan with 12 cm field of view was considered optimal for clinical fetlock imaging. Evaluation of a larger clinical population is the next step for further assessment of the clinical utility of PET imaging in horses.

18 Fluorine-fluorodeoxyglucose positron emission tomography for assessment of deep digital flexor tendinopathy: An exploratory study in eight horses with comparison to CT and MRI.

Lesions of the deep digital flexor tendon (DDFT) are a cause for foot lameness in horses. Positron emission tomography (PET) could provide valuable information regarding the metabolic activity of these lesions. The aims of this exploratory, prospective, methods comparison study were to assess the ability of 18 fluorine-fluorodeoxyglucose (18 F-FDG) PET to detect DDFT lesions and to compare the PET findings with CT and MRI findings. Eight horses with lameness due to pain localized to the front feet were included. Both front limbs of all horses were imaged with 18 F-FDG PET, noncontrast CT, and arterial contrast-enhanced CT; 11 limbs were also assessed using MRI. Two observers graded independently 18 F-FDG PET, noncontrast CT, arterial contrast CT, T1-weighted (T1-w) MRI, and T2-weighted (T2-w)/STIR MRI. Maximal standardized uptake values were measured. Lesions were found in seven of 16 DDFT on PET, 12 of 16 DDFT on noncontrast CT, six of 15 DDFT on arterial contrast CT, eight of 11 DDFT on T1-w MRI, and six of 11 DDFT on T2-w/STIR MRI. Positron emission tomography was in better agreement with arterial contrast CT (Kappa-weighted 0.40) and T2-w/STIR MRI (0.35) than with noncontrast CT (0.28) and T1-w MRI (0.20). Maximal standardized uptake values of lesions ranged from 1.9 to 4.6 with a median of 3.1. Chronic lesions with scar tissues identified on noncontrast CT or T1-w MRI did not have increased 18 F-FDG uptake. These results demonstrated that 18 F-FDG PET agreed more closely with modalities previously used to detect active tendon lesions, i.e. arterial contrast CT and T2-w/STIR MRI. 18 Fluorine-fluorodeoxyglucose PET can be used to identify metabolically active DDFT lesions in horses.

Comparison of 18F-sodium fluoride positron emission tomography and CT: An exploratory study in 12 dogs with elbow pain.

18F-Sodium Fluoride (18F-NaF) positron emission tomography (PET) provides high resolution functional information about bone activity and can be fused with CT images to improve three-dimensional localization and characterization of lesions. This prospective, observational study assessed 18F-NaF PET-CT for imaging of canine elbows, compared PET with CT findings, and assessed correlation with lameness. Twelve patients with elbow pain were included. Cases included primarily young, large breed dogs. A three-level clinical lameness score was assigned to each forelimb. All dogs had bilateral elbow joints imaged with CT and PET under general anesthesia, approximately 1.5 h after intravenous injection of 3 MBq/kg of 18F-NaF. Imaging findings were independently reviewed by two radiologists using a three-level scoring scheme over nine anatomical regions in the elbow. PET imaging identified areas of bone activity where minimal change was identified on CT. PET imaging also demonstrated absence of uptake in areas where modeling was present on CT. A stronger correlation was observed between clinical grades and PET scores (r2  = 0.38, P = .001) than between clinical grades and CT scores (r2  = 0.17, P = .048). The total PET scores were significantly different for each clinical grade (P = .013) but total CT scores did not differ (P = .139). This exploratory study suggests that PET improves the ability to detect lesions and to determine the clinical significance of CT findings in dogs with elbow pain.

POSITRON EMISSION TOMOGRAPHY OF THE EQUINE DISTAL LIMB: EXPLORATORY STUDY.

Positron emission tomography (PET) is a highly sensitive, noninvasive imaging technique for quantifying biological functions of tissues. However, at the time of this study, PET imaging applications had not been reported in the horse. The aim of this exploratory study was to determine whether a portable high-resolution PET scanner could be used to image the equine distal limb. Images of the front feet and fetlocks of three research horses, with known lesions localized to the distal front limbs, were acquired under general anesthesia after administration of 18 F-fluorodeoxyglucose (18 F-FDG), with doses ranging from 1.5 to 2.9 MBq/kg. The radiation exposure measured during imaging was slightly higher than 99m Technetium scintigraphy. However, the use of general anesthesia allowed the proximity and the contact time with the patient to be minimized for the staff involved. 18 F-FDG uptake was evident throughout the soft tissues, with the highest uptake in the coronary band and the lowest uptake in the tendons. Anatomic structures could be discriminated due to the high contrast between soft tissue and bone. Detected lesions included lysis of the flexor cortex of the navicular bone, lesions of flexor tendons and suspensory ligament, and abnormal uptake through the lamina of a laminitic subject. Findings indicated that tomographic molecular imaging is feasible in the equine distal limb and could be useful as a future diagnostic technique for clinical and research studies, especially those involving tendinopathy/desmopathy and laminitis.

Dynamic Human Brain Imaging with a Portable PET Camera: Comparison to a Standard Scanner.

Portable, cost-effective PET cameras can radically expand the applicability of PET. We present here a within-participant comparison of fully quantified [18F]FDG dynamic scans in healthy volunteers using the standard Biograph mCT scanner and portable CerePET scanner. Methods: Each of 20 healthy volunteers underwent dynamic [18F]FDG imaging with both scanners (1-154 d apart) and concurrent arterial blood sampling. Tracer SUV, net influx rate (Ki), and the corresponding cerebral metabolic rate of glucose (CMRglu) were quantified at regional and voxel levels. Results: At the regional level, CerePET outcome measure estimates within participants robustly correlated with Biograph mCT estimates in the neocortex, wherein the average Pearson correlation coefficients across participants ± SD were 0.83 ± 0.07 (SUV) and 0.85 ± 0.08 (Ki and CMRglu). There was also strong agreement between CerePET and Biograph mCT estimates, wherein the average regression slopes across participants were 0.84 ± 0.17 (SUV), 0.83 ± 0.17 (Ki), and 0.85 ± 0.18 (CMRglu). There was similar bias across participants but higher correlation and less variability in subcortical regions than in cortical regions. Pearson correlation coefficients for subcortical regions equaled 0.97 ± 0.02 (SUV) and 0.97 ± 0.03 (Ki and CMRglu), and average regression slopes equaled 0.79 ± 0.14 (SUV), 0.83 ± 0.11 (Ki), and 0.86 ± 0.11 (CMRglu). In voxelwise assessment, CerePET and Biograph mCT estimates across outcome measures were significantly different only in a cluster of left frontal white matter. Conclusion: Our results indicate robust correlation and agreement between semi- and fully quantitative brain glucose metabolism measurements from portable CerePET and standard Biograph mCT scanners. The results obtained with a portable PET scanner in this comparison in humans require follow-up but lend confidence to the feasibility of more flexible and portable brain imaging with PET.

18Oxygen Substituted Nucleosides Combined with Proton Beam Therapy: Therapeutic Transmutation In Vitro.

PURPOSE: Proton therapy precisely delivers radiation to cancers to cause damaging strand breaks to cellular DNA, kill malignant cells, and stop tumor growth. Therapeutic protons also generate short-lived activated nuclei of carbon, oxygen, and nitrogen atoms in patients as a result of atomic transmutations that are imaged by positron emission tomography (PET). We hypothesized that the transition of 18O to 18F in an 18O-substituted nucleoside irradiated with therapeutic protons may result in the potential for combined diagnosis and treatment for cancer with proton therapy. MATERIALS AND METHODS: Reported here is a feasibility study with a therapeutic proton beam used to irradiate H2 18O to a dose of 10 Gy produced by an 85 MeV pristine Bragg peak. PET imaging initiated >45 minutes later showed an 18F decay signal with T1/2 of ∼111 minutes. RESULTS: The 18O to 18F transmutation effect on cell survival was tested by exposing SQ20B squamous carcinoma cells to physiologic 18O-thymidine concentrations of 5 µM for 48 hours followed by 1- to 9-Gy graded doses of proton radiation given 24 hours later. Survival analyses show radiation sensitization with a dose modification factor (DMF) of 1.2. CONCLUSIONS: These data support the idea of therapeutic transmutation in vitro as a biochemical consequence of proton activation of 18O to 18F in substituted thymidine enabling proton radiation enhancement in a cancer cell. 18O-substituted molecules that incorporate into cancer targets may hold promise for improving the therapeutic window of protons and can be evaluated further for postproton therapy PET imaging.

Evaluation of accuracy for 18 F-FDG positron emission tomography and computed tomography for detection of lymph node metastasis in canine oral malignant melanoma.

Tumour stage has been demonstrated to have prognostic significance in canine oral malignant melanoma (OMM). Various evaluation techniques of positron emission tomography/computed tomography (PET/CT) have been reported for staging of head-and-neck tumours in people, but canine-specific data are limited, and reports for CT accuracy have been variable. In this prospective study, the head/neck of client-owned dogs with cytologically or histologically diagnosed OMM were imaged with 18 Fluorine-fluorodeoxyglucose (18 F-FDG) PET/ CT. Bilateral mandibular lymphadenectomy was performed for histopathologic assessment. Two evaluation techniques for CT and PET were applied by four independent observers. CT evaluation utilized both a standardized grading scheme and a subjective clinical interpretation. PET evaluation was first performed solely on 18 F-FDG-uptake in lymph nodes compared to background on a truncated scan excluding the oral cavity. Subsequently, the entire head/neck scan and standardized uptake value (SUV) measurements were available. Receiver operating characteristic analysis was performed with histopathology as gold standard. Twelve dogs completed the study and metastatic OMM was identified in six mandibular lymph nodes from five dogs. Of the CT-interpretation techniques, use of clinical grading performed best (sensitivity = 83% and specificity = 94%). Both PET techniques resulted in 100% sensitivity, but primary tumour site evaluation and use of SUV increased specificity from 78% to 94%. The SUVmax cut-point, 3.3, led to 100% sensitivity and 83% specificity. In this population of dogs, PET appeared to be highly sensitive but at risk of being less specific without use of appropriate parameters and thresholds.

Positron emission mammography: high-resolution biochemical breast imaging.

Positron emission mammography (PEM) provides images of biochemical activity in the breast with spatial resolution matching individual ducts (1.5 mm full-width at half-maximum). This spatial resolution, supported by count efficiency that results in high signal-to-noise ratio, allows confident visualization of intraductal as well as invasive breast cancers. Clinical trials with a full-breast PEM device have shown high clinical accuracy in characterizing lesions identified as suspicious on the basis of conventional imaging or physical examination (sensitivity 93%, specificity 83%, area under the ROC curve of 0.93), with high sensitivity preserved (91%) for intraductal cancers. Increased sensitivity did not come at a cost of reduced specificity. Considering that intraductal cancer represents more than 30% of reported cancers, and is the form of cancer with the highest probability of achieving surgical cure, it is likely that the use of PEM will complement anatomic imaging modalities in the areas of surgical planning, high-risk monitoring, and minimally invasive therapy. The quantitative nature of PET promises to assist researchers interested studying the response of putative cancer precursors (e.g., atypical ductal hyperplasia) to candidate prevention agents.

Pilot clinical trial of 18F-fluorodeoxyglucose positron-emission mammography in the surgical management of breast cancer.

BACKGROUND: High-resolution positron-emission mammography (PEM) is a new device, which allows the imaging of breast tissue. A prospective study was performed to assess the accuracy of PEM in newly diagnosed breast cancer patients. METHODS: In a prospective multicenter study, 44 women with confirmed breast cancers were imaged with a high-resolution PEM scanner (Naviscan PET Systems, Rockville, MD) with 18F-fluorodeoxyglucose. The images were blindly evaluated and were compared with final pathology. RESULTS: The majority of the index lesions were seen on PEM (89%, 39/44). PEM detected 4 of 5 incidental breast cancers, 3 of which were not seen by any other imaging modalities. Of 19 patients undergoing breast-conserving surgery, PEM correctly predicted 6 of 8 (75%) patients with positive margins and 100% (11/11) with negative margins. CONCLUSION: The current PEM device shows promise in detecting breast malignancies and may assist in the planning of adequate partial mastectomy procedures to better ensure negative margins.

Positron emission mammography: initial clinical results.

BACKGROUND: Evaluation of high-risk mammograms represents an enormous clinical challenge. Functional breast imaging coupled with mammography (positron emission mammography [PEM]) could improve imaging of such lesions. A prospective study was performed using PEM in women scheduled for stereotactic breast biopsy. METHODS: Patients were recruited from the surgical clinic. Patients were injected with 10 mCi of 2-[18F] fluorodeoxyglucose. One hour later, patients were positioned on the stereotactic biopsy table, imaged with a PEM scanner, and a stereotactic biopsy was performed. Imaging was reviewed and compared with pathologic results. RESULTS: There were 18 lesions in 16 patients. PEM images were analyzed by drawing a region of interest at the biopsy site and comparing the count density in the region of interest with the background. A lesion-to-background ratio >2.5 appeared to be a robust indicator of malignancy and yielded a sensitivity of 86%, specificity of 91%, and overall diagnostic accuracy of 89%. No adverse events were associated with the PEM imaging. CONCLUSIONS: The data show that PEM is safe, feasible, and has an encouraging accuracy rate in this initial experience. Lesion-to-background ratios >2.5 were found to be a useful threshold value for identifying positive (malignant) results. This study supports the further development of PEM.