Hilmar Kuehl

Accuracy of Whole-Body Dual-Modality Fluorine-18–2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) for Tumor Staging in Solid Tumors: Comparison With CT and PET

PURPOSE To assess the accuracy of positron emission tomography/computed tomography (PET/CT) when staging different malignant diseases. PATIENTS AND METHODS This was a retrospective, blinded, investigator-initiated study of 260 patients with various oncological diseases who underwent fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT for tumor staging. CT images alone, PET images alone, PET + CT data viewed side by side, and fused PET/CT images were evaluated separately according to the tumor-node-metastasis system. One hundred forty patients with tumors not staged according to the tumor-node-metastasis system or a lack of reference standard were excluded from data analysis; 260 patients were included. Diagnostic accuracies were determined for each of the four image sets. Histopathology and a clinical follow-up of 311 (+/- 125) days served as standards of reference. RESULTS PET/CT proved significantly more accurate in assessing tumor-node-metastasis system stage compared with CT alone, PET alone, and side-by-side PET + CT (P < .0001). Of 260 patients, 218 (84%; 95% CI, 79% to 88%) were correctly staged with PET/CT, 197 (76%; 95% CI, 70% to 81%) with side-by-side PET + CT, 163 (63%; 95% CI, 57% to 69%) with CT alone, and 166 (64%; 95% CI, 58% to 70%) with PET alone. Combined PET/CT had an impact on the treatment plan in 16, 39, and 43 patients when compared with PET + CT, CT alone, and PET alone, respectively. CONCLUSION Tumor staging with PET/CT is significantly more accurate than CT alone, PET alone, and side-by-side PET + CT. This diagnostic advantage translates into treatment plan changes in a substantial number of patients.

The impact of 68Ga-DOTATOC positron emission tomography/computed tomography on the multimodal management of patients with neuroendocrine tumors.

Objective:To evaluate the impact of 68Ga-DOTATOC positron emission tomography (PET)/computed tomography (CT) on the multimodal management of neuroendocrine tumors (NET). Background:Establishment of the extent and progression of NET are necessary to decide which treatment option to choose. However, morphological imaging with CT or magnetic resonance imaging (MRI) is often inadequate in identifying the primary tumor and/or in detecting small metastatic lesions. Methods:In total, 52 patients (27 women and 25 men) with histologically proven NET could be included in the protocol of comparison between 68Ga-DOTATOC PET/CT and CT and/or MRI. The examinations were performed in terms of tumor staging and, in some instances, also of primary tumor site identification to evaluate the patients eligibility for treatment. Each patient presented with either CT and/or MRI performed elsewhere and consecutively underwent 68Ga-DOTATOC PET/CT in our institution. Results:In all 52 patients, 68Ga-DOTATOC PET/CT demonstrated pathologically increased uptake for at least 1 tumor site, yielding a sensitivity of 100% on a patient basis. In 3 of 4 patients with unknown primary tumor site, 68Ga-DOTATOC PET/CT visualized the primary tumor region (jejunum, ileum, and pancreas, respectively) not identified on CT and/or MRI. 68Ga-DOTATOC PET/CT detected additional hepatic and/or extrahepatic metastases in 22 of the 33 patients diagnosed with hepatic metastases on CT and/or MRI. Of the 15 patients evaluated for liver transplantation, we omitted 7 (46.6%) from further screening because of evidence of metastatic deposits not seen by conventional imaging. Overall, 68Ga-DOTATOC PET/CT altered our treatment decision based on CT and/or MRI alone, in 31 (59.6%) of the 52 patients. Conclusions:In this study, 68Ga-DOTATOC PET/CT proved clearly superior to CT and/or MRI for detection and staging of NET. More important, 68Ga-DOTATOC PET/CT impacted our treatment decision in more than every second patient.

Interventional magnetic resonance angiography with no strings attached: wireless active catheter visualization.

Active instrument visualization strategies for interventional MR angiography (MRA) require vascular instruments to be equipped with some type of radiofrequency (RF) coil or dipole RF antenna for MR signal detection. Such visualization strategies traditionally necessitate a connection to the scanner with either coaxial cable or laser fibers. In order to eliminate any wire connection, RF resonators that inductively couple their signal to MR surface coils were implemented into catheters to enable wireless active instrument visualization. Instrument background to contrast‐to‐noise ratio was systematically investigated as a function of the excitation flip angle. Signal coupling between the catheter RF coil and surface RF coils was evaluated qualitatively and quantitatively as a function of the catheter position and orientation with regard to the static magnetic field B0 and to the surface coils. In vivo evaluation of the instruments was performed in interventional MRA procedures on five pigs under MR guidance. Cartesian and projection reconstruction TrueFISP imaging enabled simultaneous visualization of the instruments and vascular morphology in real time. The implementation of RF resonators enabled robust visualization of the catheter curvature to the very tip. Additionally, the active visualization strategy does not require any wire connection to the scanner and thus does not hamper the interventionalist during the course of an intervention. Magn Reson Med 53:446–455, 2005.

Inductively coupled stent antennas in MRI

The development of intimal hyperplasia following stent deployment can lead to narrowing or even occlusion of the stent lumen. The underlying mechanisms leading to neointimal proliferation within stents remain largely unknown. Long‐term evaluation of stent patency requires a noninvasive means for assessing the stent lumen. MR angiography (MRA) has shown potential to provide noninvasive assessment of the vascular system. However, a detailed assessment of the stent lumen with MRI is often hampered by material‐dependent susceptibility artifacts, as well as by radiofrequency (RF) eddy currents generated inside the electrically conducting stent mesh. In this study, stent prototypes were designed to act as active resonant structures at the Larmor frequency of the MR system. Employing the principle of inductive coupling, the B1 fields of the stents were coupled to that of an outside surface coil. The stents thus acted as local RF signal amplifiers. Various stent designs were investigated regarding their coupling to an external coil, signal homogeneity, and suitability for mechanical expansion for implantation purposes. The dependency of flip angle amplification on the quality factor Q of the stents was systematically investigated. Phantom experiments revealed signal amplification in all stent prototypes. Signal enhancement inside and close to the surface of the stents enabled their localization with high contrast in MR images. In vivo imaging experiments in the iliac, renal, and splenic arteries of two pigs confirmed the in vitro findings. Wireless active visualization of stents allows for detailed analysis of the stent lumen with high contrast and spatial resolution. The proposed method could thus provide a powerful diagnostic means for the noninvasive long‐term follow‐up of stent patency, thereby enhancing our understanding of the mechanisms of restenosis. Magn Reson Med 48:781–790, 2002.

Interventional MRA using actively visualized catheters, TrueFISP, and real‐time image fusion

An integrated system for performing interventional magnetic resonance angiography (MRA) with actively visualized instruments and real‐time image fusion was implemented on a 1.5 T scanner. True fast imaging with steady precession (TrueFISP) imaging provided high acquisition speed paired with high signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) for the simultaneous visualization of active instruments and arterial morphology. The system enabled simultaneous image reconstruction and image postprocessing of multiple receiver channels, with subsequent image fusion display in real time. Optional interleaved image acquisition in two planes provided additional important information for biplanar instrument guidance. Various vascular interventions, including selective catheterization and subsequent selective MRA of the abdominal aorta, renal arteries, superior mesenteric artery (SMA), hepatic artery, and aortic arch, were performed on 10 pigs under MR guidance. In terms of instrument contrast, image acquisition, reconstruction, and fusion speed, the setup represents a powerful platform for performing interventional MRA procedures. Magn Reson Med 49:129–137, 2003.

Depiction and characterization of liver lesions in whole body [18F]-FDG PET/MRI

OBJECTIVES To assess the value of PET/MRI with [(18)F]-FDG using a whole body protocol for the depiction and characterization of liver lesions in comparison to PET/CT. METHODS 70 patients (31 women, 39 men) with solid tumors underwent [(18)F]-FDG PET/CT and followed by an additional PET/MRI using an integrated scanner. Two readers rated the datasets (PET/CT; PET/MRI) regarding conspicuity of hepatic lesions (4-point ordinal scale) and diagnostic confidence (5-point ordinal scale). Median scores for lesion conspicuity and diagnostic confidence were compared using Wilcoxons rank sum test. Prior examinations, histopathology and clinical follow-up (116 ± 54 days) served as standard of reference. RESULTS 36 of 70 (51%) patients showed liver lesions. Using PET/CT and PET/MRI all patients with liver metastases could correctly be identified. A total of 97 lesions were found (malignant n=26; benign n=71). For lesion conspicuity significantly higher scores were obtained for PET/MRI in comparison to PET/CT (p<0.001). Significantly better performance for diagnostic confidence was observed in PET/MRI, both for malignant as for benign lesions (p<0.001). CONCLUSIONS PET/MRI, even in the setting of a whole body approach, provides higher lesion conspicuity and diagnostic confidence compared to PET/CT and may therefore evolve as an attractive alternative in oncologic imaging.

Simultaneous 68Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic neuroendocrine tumors: initial results.

ObjectivesThe aim of this pilot study was to demonstrate the potential of simultaneously acquired 68-Gallium-DOTA-D-Phe1-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison with 68Ga-DOTATOC PET/computed tomography (PET/CT) in patients with known gastroenteropancreatic neuroendocrine tumors (NETs). Materials and MethodsEight patients (4 women and 4 men; mean [SD] age, 54 [17] years; median, 55 years; range 25–74 years) with histopathologically confirmed NET and scheduled 68Ga-DOTATOC PET/CT were prospectively enrolled for an additional integrated PET/MRI scan. Positron emission tomography/computed tomography was performed using a triple-phase contrast-enhanced full-dose protocol. Positron emission tomography/magnetic resonance imaging encompassed a diagnostic, contrast-enhanced whole-body MRI protocol. Two readers separately analyzed the PET/CT and PET/MRI data sets including their subscans in random order regarding lesion localization, count, and characterization on a 4-point ordinal scale (0, not visible; 1, benign; 2, indeterminate; and 3, malignant). In addition, each lesion was rated in consensus on a binary scale (allowing for benign/malignant only). Clinical imaging, existing prior examinations, and histopathology (if available) served as the standard of reference. In PET-positive lesions, the standardized uptake value (SUVmax) was measured in consensus. A descriptive, case-oriented data analysis was performed, including determination of frequencies and percentages in detection of malignant, benign, and indeterminate lesions in connection to their localization. In addition, percentages in detection by a singular modality (such as PET, CT, or MRI) were calculated. Interobserver variability was calculated (Cohens &kgr;). The SUVs in the lesions in PET/CT and PET/MRI were measured, and the correlation coefficient (Pearson, 2-tailed) was calculated. ResultsAccording to the reference standard, 5 of the 8 patients had malignant NET lesions at the time of the examination. A total of 4 patients were correctly identified by PET/CT, with the PET and CT component correctly identifying 3 patients each. All 5 patients positive for NET disease were correctly identified by PET/MRI, with the MRI subscan identifying all 5 patients and the PET subscan identifying 3 patients. All lesions considered as malignant in PET/CT were equally depicted in and considered using PET/MRI. One liver lesion rated as “indetermined” in PET/CT was identified as metastasis in PET/MRI because of a diffusion restriction in diffusion-weighted imaging. Of the 4 lung lesions characterized in PET/CT, only 1 was depicted in PET/MRI. Of the 3 lymph nodes depicted in PET/CT, only 1 was characterized in PET/MRI. Interobserver reliability was equally very good in PET/CT (&kgr; = 0.916) and PET/MRI (&kgr; = 1.0). The SUVmax measured in PET/CT and in PET/MRI showed a strong correlation (Pearson correlation coefficient, 0.996). ConclusionsThis pilot study demonstrates the potential of 68Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic NET, with special advantages in the characterization of abdominal lesions yet certain weaknesses inherent to MRI, such as lung metastases and hypersclerotic bone lesions.

Comparison of FDG-PET, PET/CT, and MRI for follow-up of colorectal liver metastases treated with radiofrequency ablation: initial results

PURPOSE Morphologic imaging after radiofrequency ablation (RFA) of liver metastases is hampered by rim-like enhancement in the ablation margin, making the identification of local tumor progression (LTP) difficult. Follow-up with PET/CT is compared to follow-up with PET alone and MRI after RFA. METHODS AND MATERIALS Sixteen patients showed 25 FDG-positive colorectal liver metastases in pre-interventional PET/CT. Post-interventional PET/CT was performed 24h after ablation and was repeated after 1, 3 and 6 months and then every 6 months. PET and PET/CT data were compared with MR data sets acquired within 14 days before or after these time points. Either histological proof by biopsy or resection, or a combination of contrast-enhanced CT at fixed time points and clinical data served as a reference. RESULTS The 25 metastases showed a mean size of 20mm and were treated with 39 RFA sessions. Ten lesions which developed LTP received a second round of RFA; four lesions received three rounds of treatment. The mean follow-up time was 22 months. Seventy-two PET/CT and 57 MR examinations were performed for follow-up. The accuracy and sensitivity for tumor detection was 86% and 76% for PET alone, 91% and 83% for PET/CT and 92% and 75% for MRI, respectively. CONCLUSIONS In comparison to PET alone, PET/CT was significantly better for detecting LTP after RFA. There were no significant differences between MRI and PET/CT. These preliminary results, however, need further verification.

Preoperative assessment of hilar cholangiocarcinoma by dual-modality PET/CT.

The purpose of the current study was to evaluate the accuracy of 18F‐FDG PET/CT in staging hilar cholangiocarcinoma.

Correlation of PET/CT Findings and Histopathology after Neoadjuvant Therapy in Non-Small Cell Lung Cancer

Objectives: Prediction of histopathological response with PET/CT scans after neoadjuvant chemoradiotherapy is limited by confounding factors which have been evaluated in this analysis. Methods:18F-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT findings [standard uptake value (SUV), residual tumor volume] were correlated with histopathological parameters of the resection specimens (tumor cell density, necrosis, scar, macrophage infiltration) in patients with locally advanced non-small cell lung cancer (stage IIIA/IIIB) after neoadjuvant induction chemotherapy (platinum-based doublet) and concurrent chemoradiotherapy (cisplatin/vinorelbine/45 Gy). Results: Sixty patients [40 male/20 female, median age 56 years (34–78)] completed induction therapy, 46 patients (stage IIIA/IIIB: 16/30; squamous cell carcinoma 41%, adenocarcinoma 48%, large cell carcinoma 11%) were resected. Pathologic complete response of the primary tumor was observed in 19 patients (41%) with a broad range of SUVmean (0.4–9.8, mean 3.0) after neoadjuvant therapy. A high rate of histopathological complete remissions (44%) was observed in tumors with a postinduction SUV >2.5 and volumes larger than the median (7.9 cm3) before resection. SUVmean was positively correlated with the macrophage score (r = 0.39, p = 0.007) and tumor cell density (r = 0.32, p = 0.03). Conclusions: These observations suggest that postinduction FDG uptake should be interpreted with caution in larger residual tumor volumes, since high SUV levels may be due to macrophage infiltration and not viable tumor tissue.