Alex Frenkel

Super-resolution in PET imaging

This paper demonstrates a super-resolution method for improving the resolution in clinical positron emission tomography (PET) scanners. Super-resolution images were obtained by combining four data sets with spatial shifts between consecutive acquisitions and applying an iterative algorithm. Super-resolution attenuation corrected PET scans of a phantom were obtained using the two-dimensional and three-dimensional (3-D) acquisition modes of a clinical PET/computed tomography (CT) scanner (Discovery LS, GEMS). In a patient study, following a standard /sup 18/F-FDG PET/CT scan, a super-resolution scan around one small lesion was performed using axial shifts without increasing the patient radiation exposure. In the phantom study, smaller features (3 mm) could be resolved axially with the super-resolution method than without (6 mm). The super-resolution images had better resolution than the original images and provided higher contrast ratios in coronal images and in 3-D acquisition transaxial images. The coronal super-resolution images had superior resolution and contrast ratios compared to images reconstructed by merely interleaving the data to the proper axial location. In the patient study, super-resolution reconstructions displayed a more localized /sup 18/F-FDG uptake. A new approach for improving the resolution of PET images using a super-resolution method has been developed and experimentally confirmed, employing a clinical scanner. The improvement in axial resolution requires no changes in hardware.

The additional value of PET/CT over PET in FDG imaging of oesophageal cancer

PurposeThe aim of this study was to assess the value of combined PET/CT compared with PET reviewed side-by-side with CT, in patients with oesophageal cancer, before and after surgery.MethodsForty-one FDG PET/CT studies were performed in 32 patients with oesophageal cancer, before surgery (n=18) or during follow-up after resection of the primary tumour (n=23). One hundred and fifteen sites suspicious for malignancy were evaluated. PET/CT was prospectively compared with PET reviewed side-by-side with CT, for detection, accurate localisation and characterisation of malignant sites. PET/CT performance in different anatomical regions was compared before and after surgery. The impact of fused data on patient management was retrospectively assessed.Results PET/CT had an incremental value over PET for interpretation of 25 of 115 sites (22%), changing the initial characterisation of ten sites to either malignant (n=1) or benign (n=9), and defining the precise anatomical location of 15 sites. PET/CT provided better specificity and accuracy than PET for detecting sites of oesophageal cancer (81% and 90% vs 59% and 83% respectively, p<0.01). Fusion was of special value for interpretation of cervical and abdomino-pelvic sites, for disease assessment in loco-regional lymph nodes before surgery and in regions of postoperative anatomical distortion. PET/CT had an impact on the further management of four patients (10%), by detecting nodal metastases that warranted disease upstaging (n=2) and by excluding disease in sites of benign uptake after surgery (n=2).ConclusionPET/CT improves the accuracy of FDG imaging in oesophageal cancer and provides data of diagnostic and therapeutic significance for further patient management.

Correction of Heart Motion Due to Respiration in Clinical Myocardial Perfusion SPECT Scans Using Respiratory Gating

Several studies have described nonuniform blurring of myocardial perfusion imaging (MPI) due to respiration. This article describes a technique for correcting the respiration effect and assesses its effectiveness in clinical studies. Methods: Simulated phantoms, physical phantoms, and patient scans were used in this study. A heart phantom, which oscillated back and forth, was used to simulate respiration. The motion was measured on a γ-camera supporting list-mode functionality synchronized with an external respiratory strap or resistor sensor. Eight clinical scans were performed using a 1-d 99mTc-sestamibi protocol while recording the respiratory signal. The list-mode capability along with the strap or sensor signals was used to generate respiratory bin projection sets. A segmentation process was used to detect the shift between the respiratory bins. This shift was further projected to the acquired projection images for correction of the respiratory motion. The process was applied to the phantom and patient studies, and the rate of success of the correction was assessed using the conventional bulls eye maps. Results: The algorithm provided a good correction for the phantom studies. The shift after the correction, measured by a fitted ellipsoid, was <1 mm in the axial direction. The average motion due to respiration in the clinical studies was 9.1 mm in the axial direction. The average shift between the respiratory phases was reduced to 0.5 mm after correction. The maximal change in the bulls eye map for the clinical scans after the correction was 6%, with a mean of 3.75%. The postcorrection clinical summed perfusion images were more uniform, consistent, and, for some patients, clinically significant when compared with the images before correction for respiration. Conclusion: Myocardial motion generated by respiration during MPI SPECT affects perfusion image quality and accuracy. Motion introduced by respiration can be corrected using the proposed method. The degree of correction depends on the patient respiratory pattern and can be of clinical significance in certain cases.

Single-photon emission computed tomography quantitation of gallium citrate uptake for the differentiation of lymphoma from benign hilar uptake

PURPOSE To assess the role of quantitative gallium citrate (Ga 67) single-photon emission computed tomography (SPECT) in differentiating lymphoma from benign hilar uptake, concentrations of Ga 67 in 29 sites of documented lymphoma and in 75 benign lesions were compared. PATIENTS AND METHODS One hundred seven thoracic Ga 67 SPECT studies obtained in 101 consecutive lymphoma patients were reviewed. Fifty-nine studies detected Ga 67 uptake in the hilar and or mediastinal regions. Forty-eight studies showed no such abnormality. The concentration of Ga 67 in the thoracic lesions was measured using a quantitative SPECT technique and its nature was determined by correlation with computed tomographic (CT) scans and follow-up evaluation of the sites. RESULTS In 20 of 59 abnormal studies (34%), there was lymphoma in the hilar and or mediastinal regions. In the remaining 39 abnormal studies (66%), Ga 67 uptake was benign. There were 29 sites of lymphoma and 75 benign lesions. The concentration of Ga 67 in lymphoma was significantly higher than in benign hilar uptake (13.2 +/- 5.4 %ID/mL x 10(-3) v 5.6 +/- 1.5 % injected dose (ID)/mL x 10(-3); P < .001). A concentration value of 8.3 %ID/mL x 10(-3) was found to best separate lymphoma and benign uptake, with a sensitivity of 90%, a specificity of 93%, a positive predictive value of 84%, and a negative predictive value of 96%. CONCLUSION Lymphoma and benign hilar uptake differ significantly in their concentration of Ga 67. The present study shows that quantitative Ga-67 SPECT reliably differentiates lymphoma and benign uptake.

A practical SPECT technique for quantitation of drug delivery to human tumors and organ absorbed radiation dose

A practical quantitative single photon emission computed tomographic (SPECT) technique based on an empirical threshold analysis permits accurate measurements in humans of drug delivery and absorbed radiation dose. The limits of the method have been explored using a wide range of phantom volumes, concentrations, and target-to-nontarget ratios. A threshold of 43% was found to give the best results using volumes of 30 to 3,800 cc. An excellent correlation (r = .99 with a standard error of estimate [SEE] of 41 cc) was found between SPECT measured volumes and actual phantom volumes. A similarly high correlation (r = .98, SEE = 260 counts/voxel) was found in 77 measurements of concentrations between 0.01 and 3.6 microCi/cc. There was a direct relationship between the target-to-nontarget ratio of phantoms and the accuracy of volume measurements. The technique has been validated by an excellent in vivo/in vitro correlation of uptake in human tumors. The tumor cumulative concentration and tumor-to-blood ratio were used for assessment of drug delivery. In vivo quantitative measurements of the pharmacokinetics of technetium-99m (99mTc) glucoheptonate, cobalt-57 (57Co) bleomycin and platinum-195m (195mPt) cisplatin in human tumors in vivo indicates that, in contrast with tumor models in animals, there is a marked variability in drug delivery even in tumors with the same histology. Future development of labeled drugs should make it possible to use quantitative SPECT for predicting tumor response to therapy and for tailoring chemotherapy for the individual patient under treatment. SPECT quantitation of organ concentration was used for Medical Internal Radiation Dose committee (MIRD) calculations of organ absorbed radiation dose from 99mTc-labeled RBCs. Excellent in vivo/in vitro correlations were obtained between SPECT measured concentrations of blood radioactivity in the heart and in vitro measurements of blood samples. The possibilities and limitations of this technique are discussed and its use for in vivo measurement in humans of absorbed radiation dose from radiopharmaceuticals is suggested.

Physiologic Thymic Uptake of 18F-FDG in Children and Young Adults: A PET/CT Evaluation of Incidence, Patterns, and Relationship to Treatment

18F-FDG uptake in the thymus, mainly related to hyperplasia after chemotherapy, has been described. Thymic uptake can challenge the accurate assessment of cancer patients by 18F-FDG imaging. The present study defines the incidence, patterns, and intensity of thymic 18F-FDG uptake in relationship to age and time after treatment in a large cohort of patients. Methods: A total of 559 consecutive 18F-FDG PET/CT studies in 160 patients (86 men, 74 women; age, 3–40 y) performed at baseline, during treatment, at the end of treatment, and during follow-up were retrospectively reviewed. PET/CT studies were assessed for the presence or absence (T+ or T−, respectively), pattern, and intensity (SUVmax) of increased 18F-FDG uptake in the anterior mediastinum, localized by the CT component to the thymus. The overall incidence of 18F-FDG avidity in the thymus in relationship to the patients age and time after treatment administration were statistically evaluated. Results: There were 137 of 559 T+ studies (25%), with equal sex distribution. T+ studies were found in significantly younger patients (20.6 ± 9.3 y vs. 27.4 ± 8.4 y, P < 0.001). Most T+ patients (60%) showed an inverted V pattern of thymic uptake, with additional unilateral mediastinal extension in 24% and focal midline uptake in 16% of studies. T+ studies were encountered in 80% of patients younger than 10 y, compared with 8% of patients in the 31- to 40-y age group. There were 17% T+ studies at baseline, 6% during treatment, 8% at the end of treatment, and 27%–40% during follow-up. The average SUVmax of thymic 18F-FDG uptake was 3.73 ± 1.22. Conclusion: Thymic 18F-FDG uptake was found in 28% of the present study population, more frequently after treatment. T+ patients were significantly younger. Thymic uptake was found in 73% of untreated patients up to the age of 13 y and in 8% of patients in the fourth decade of life. Knowledge of this age- and treatment-related incidence of physiologic thymic 18F-FDG avidity can reduce the number of potential pitfalls in reporting PET/CT studies in cancer patients.

The reduction of artifacts due to metal hip implants in CT-attenuation corrected PET images from hybrid PET/CT scanners

CT beam hardening artifacts near metal hip implants may erroneously enhance or diminish radiotracer uptake following CT attenuation correction (AC) of PET images. An artifact reduction algorithm (ARA) was developed to reduce metal artifacts in CT-based AC-PET. The algorithm employed a Bayes classifier to identify beam-hardening artifacts, followed by a partial correction of the attenuation map. ARA was implemented on phantom and patient 18F-FDG studies using a clinical PET/CT scanner. In phantom studies ARA successfully removed two artifacts of erroneously elevated uptake near a stainless steel hip prosthesis which were depicted in the standard CT-AC PET. ARA has also identified two targets absent on the scanner PET images. Target-to-background ratios were 1.5–3 times higher for ARA-PET than scanner images. In a patient study, metal artifacts were of lower intensity in ARA-PET as compared to standard images. Potentially, ARA may improve detectability of small lesions located near metal hip implants.

Improved image fusion in PET/CT using hybrid image reconstruction and super-resolution.

Purpose. To provide PET/CT image fusion with an improved PET resolution and better contrast ratios than standard reconstructions. Method. Using a super-resolution algorithm, several PET acquisitions were combined to improve the resolution. In addition, functional PET data was smoothed with a hybrid computed tomography algorithm (HCT), in which anatomical edge information taken from the CT was employed to retain sharper edges. The combined HCT and super-resolution technique were evaluated in phantom and patient studies using a clinical PET scanner. Results. In the phantom studies, 3 mm18F-FDG sources were resolved. PET contrast ratios improved (average: 54%, range: 45%–69%) relative to the standard reconstructions. In the patient study, target-to-background ratios also improved (average: 34%, range: 17%–47%). Given corresponding anatomical borders, sharper edges were depicted. Conclusion. A new method incorporating super-resolution and HCT for fusing PET and CT images has been developed and shown to provide higher-resolution metabolic images.

Directions and Magnitudes of Misregistration of CT Attenuation-Corrected Myocardial Perfusion Studies: Incidence, Impact on Image Quality, and Guidance for Reregistration

CT-based attenuation-corrected (AC) myocardial perfusion imaging (MPI) studies may show significant artifacts caused by misregistration between SPECT and CT data. The present study aimed at identifying the directions and magnitudes of misregistration with greatest impact on AC myocardial perfusion image quality. Methods: The incidence, magnitude, and direction of misregistration were assessed in 248 consecutive stress–rest MPI studies in 124 patients. In addition, cardiac SPECT/CT registration was artificially modified in 40 studies, shifting CT data by ±1, ±2, and ±3 pixels along the cephalad/caudal, dorsal/ventral, and left/right axes. Percentage of change in 5-wall AC-MPI polar map scoring was calculated for each region, and the direction of the shift along each axis was analyzed statistically (Student t test, P < 0.05) and compared to determine the region most significantly affected by each shift (Newman–Keuls test, P < 0.05). Changes in the normal and abnormal summed stress score (SSS) due to artificial misregistration were assessed (κ-statistics, McNemar differences). Results: SPECT/CT misregistration of more than 1 pixel was found in 73% (181/248) of studies and more than 2 pixels in 23% of studies (57/248). A 3-pixel ventral shift most significantly affected polar map scoring (−15.4% ± 6.1% change in lateral wall; −7.5% ± 5.5% change in inferior wall). A 3-pixel dorsal shift resulted in a −9.5% ± 5.3% apical and −8.8% ± 5.8% septal change. Polar map scoring was least affected by the cephalad/caudal shift (<5% average change in all regions except for the anterior wall; −9.9% ± 7.4% change for 3-pixel caudal shift). The most significant changes occurred in the lateral and anterior walls when the myocardium on SPECT overlapped lung tissue on CT, encountered in 16% of studies (40/248). Clinically significant changes (in SSS) occurred for the 3-pixel caudal, dorsal, and right shifts. Conclusion: A misregistration of significant magnitude occurred in 23% of studies and in the direction of the most severe artifacts in 16% of studies. Severe misregistration along the dorsal/ventral axis most significantly affected AC-MPI. Quality control of SPECT and CT registration and manual realignment should be performed routinely, with the highest priority in AC studies showing an overlay of the myocardium on SPECT with lung tissue on the CT component of AC-MPI.

Tumor Aggressiveness and Patient Outcome in Cancer of the Pancreas Assessed by Dynamic 18F-FDG PET/CT

This study aimed to assess the role of a quantitative dynamic PET model in pancreatic cancer as a potential index of tumor aggressiveness and predictor of survival. Methods: Seventy-one patients with 18F-FDG–avid adenocarcinoma of the pancreas before treatment were recruited, including 27 with localized tumors (11 underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with metastatic disease. Dynamic 18F-FDG PET images were acquired over a 60-min period, followed by a whole-body PET/CT study. Quantitative data measurements were based on a 2-compartment model, and the following variables were calculated: VB (fractional blood volume in target area), K1 and k2 (kinetic membrane transport parameters), k3 and k4 (intracellular 18F-FDG phosphorylation and dephosphorylation parameters, respectively), and 18F-FDG INF (global 18F-FDG influx). Results: The single significant variable for overall survival (OS) in patients with localized disease was 18F-FDG INF. Patients with a high 18F-FDG INF (>0.033 min−1) had a median OS of 6 and 5 mo for nonresectable and resected tumors, respectively, versus 15 and 19 mo for a low 18F-FDG INF in nonresectable and resected tumors, respectively (P < 0.04). In metastatic disease, multivariate analysis found VB, K1, and k3 to be significant variables for OS (P < 0.043, <0.031, and <0.009, respectively). Prognostic factors for OS in the entire group of patients that were significant at multivariate analysis were stage of disease, VB, K1, and 18F-FDG INF (P < 0.00035, <0.03, <0.024, and <0.008, respectively). Median OS for all patients with a high 18F-FDG INF, low VB, and high K1 was 3 mo, as opposed to 14 mo in patients with a low 18F-FDG INF, high VB, and low K1 (P < 0.021), irrespective of stage and resectability. Conclusion: Quantitative 18F-FDG kinetic parameters measured by dynamic PET in newly diagnosed pancreatic cancer correlated with the aggressiveness of disease. The 18F-FDG INF was the single most significant variable for OS in patients with localized disease, whether resectable or not.