Neuroendocrine tumor recurrence: diagnosis with 68Ga-DOTATATE PET/CT.

PURPOSE: To evaluate diagnostic performance of gallium 68-tetraazacyclododecane tetraacetic acid-octreotate ((68)Ga-DOTATATE) in detection of recurrent neuroendocrine tumors (NETs). MATERIALS AND METHODS: Approval was waived by the local ethics committee for this retrospective study. Between 2007 and 2011, 63 patients (mean age, 58 years) were examined with (68)Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) after primary NET curative resection. Reasons for PET/CT were regular follow-up examinations (n = 30), increased plasma levels of tumor markers (n = 27), or clinical suspicion of recurrence (n = 6). Final diagnosis was determined with histopathologic verification (n = 25) or clinical follow-up (n = 38). PET/CT scans were evaluated in consensus by two readers without blinding to clinical information and independently by two readers with blinding. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Final diagnosis of NET recurrence was determined in 29 patients. In three other patients, tumors of nonneuroendocrine origin were diagnosed. (68)Ga-DOTATATE PET/CT helped identify NET recurrence in 26 of 29 patients (sensitivity, 90%) and exclude presence of recurrent NET in 28 of 34 patients (specificity, 82% ). PET/CT provided false-positive and false-negative results in six and three patients (PPV, 81% [26 of 32]; NPV, 90% [28 of 31]; accuracy, 86% [54 of 63]). In gastroenteropancreatic NET (n = 45), sensitivity was 94% (17 of 18); specificity was 89% (24 of 27); PPV was 85% (17 of 20); NPV was 96% (24 of 25); and accuracy was 91% (41 of 45). Two blinded readers achieved sensitivity of 79% (23 of 29) and 76% (22 of 29); specificity of 85% (29 of 34) and 94% (32 of 34) (κ = 0.80); and accuracy of 83% and 86%. CONCLUSION: (68)Ga-DOTATATE PET/CT is accurate in detection of recurrent NET. Blinded PET/CT review markedly decreased sensitivity, underlining importance of considering clinical parameters in NET recurrence. Present results must be further validated to substantiate use of (68)Ga-DOTATATE PET/CT in routine follow-up after curative resection of NET.

Tumor load in patients with multiple myeloma: ß2-microglobulin levels versus whole-body MRI.

OBJECTIVE: Beta-2-microglobulin is a serum maker of tumor burden in hematologic malignancies. We aimed to correlate serum ß2-microglobulin levels in patients with multiple myeloma (MM) to tumor mass determined by whole-body MRI. MATERIALS AND METHODS: We retrospectively included patients with newly diagnosed, untreated MM who underwent whole-body MRI at our institution between 2003 and 2011. Patients with a glomerular filtration rate of less than 60 mL/min were excluded from analysis because ß2-microglobulin levels are increased in renal failure. Thirty patients could be included. Whole-body MRI examinations (T1-weighted turbo spin-echo and STIR sequences) were assessed by two musculoskeletal radiologists in consensus for focal lesions and the presence of diffuse myeloma infiltration. The presence of diffuse infiltration was confirmed by histology as the reference standard. MM was staged according to the Durie and Salmon PLUS staging system. RESULTS: According to whole-body MRI findings, MM was classified as Durie and Salmon PLUS stage I (low grade) in 13 patients, stage II (intermediate grade) in six patients, and stage III (high grade) in 11 patients. As we expected, most patients with stage I disease (12/13) had normal ß2-microglobulin levels (≤ 3 mg/L). Higher ß2-microglobulin values were associated with a higher stage of disease (p < 0.05). However, five of six patients with stage II MM and five of 11 patients with stage III MM showed normal ß2-microglobulin levels. Thus, 10 of 17 patients (58.8%) with substantial infiltration in the bone marrow showed false-negative ß2-microglobulin levels. CONCLUSION: Serum ß2-microglobulin levels correlate with tumor stage in MM. However, it may be misleading as a marker of tumor load in a subset of patients with substantial myeloma infiltration in the bone marrow. Whole-body MRI may display the full tumor load and correctly show the extension of myeloma infiltrates.

Quantitative analysis of vertebral bone marrow perfusion using dynamic contrast-enhanced MRI: initial results in osteoporotic patients with acute vertebral fracture.

PURPOSE: To evaluate the potential of quantitative dynamic contrast-enhanced MRI (DCE-MRI) in vertebral bone marrow (vBM) of patients with acute osteoporotic vertebral compression fractures. MATERIALS AND METHODS: Twenty-six patients with acute osteoporotic fractures (16 female, 10 male, median age 72, range 48-89) and 10 subjects without known history of osteoporosis (6 female, 4 male, median 65, range 31-77) were examined 2D-DCE-MRI. Region of interest (ROI) data in fractured (n = 26) and normal-appearing vertebrae (n = 271) were analyzed with a two-compartment tracer-kinetic-model, providing estimates of at least three independent parameters: plasma flow (PF), plasma volume (PV), and extraction flow (EF). Parameters were correlated with dual x-ray absorptiometry (DXA) (n = 15) and quantitative computed tomography (QCT) densitometry (n = 10). RESULTS: Mean PF was significantly higher in fractures than in normal-appearing vertebrae (69.37 vs. 11.72 mL/100 mL/min). Similarly, mean PV and EF differed significantly. Mean PF was significantly decreased in normal-appearing vBM osteoporotic patients compared to the control group. Mean PF and PV were significantly decreased in lumbar compared to thoracic vertebrae. PV showed a significant correlation with QCT. CONCLUSION: Perfusion parameters were decreased significantly in normal-appearing vBM of patients. Furthermore, significant perfusion alterations were observed in acute osteoporotic vertebral fractures compared to normal-appearing vertebrae.

Correlation between vacuum phenomenon on CT and fluid on MRI in degenerative disks.

OBJECTIVE: The purpose of this study is to correlate the presence of intradiscal vacuum phenomenon on CT to that of intradiscal fluid on MRI. SUBJECTS AND METHODS: In a prospective study, 20 patients with lumbar vacuum phenomenon on CT underwent two MRI examinations. One was performed after mobilization, and the other was performed after 6 hours of bed rest. T2-weighted turbo-spin echo (TSE), STIR, T1-weighted TSE, and four consecutive T2-weighted TSE sequences were performed on a 1.5-T scanner. Ninety-five discal segments were assessed for the presence of intradiscal fluid or hyperintense signal on the T2-weighted MRI examinations and were correlated with the presence of vacuum phenomenon on CT, degenerative endplate abnormalities on CT, and edema on MRI. RESULTS: Sixty-nine of 95 discal segments (72.6%) showed vacuum phenomenon on CT. Sixteen of those 69 discal segments (23.1%) showed intradiscal fluid (n = 12) or hyperintense signal (n = 4) on MRI examinations performed after mobilization. Forty-one of 69 discal segments (59.4%) with vacuum phenomenon showed intradiscal fluid (n = 29) or hyperintense signal (n = 12) on MRI examinations performed after bed rest. Seventeen segments showed only fluid after bed rest. Nine segments showed more fluid after bed rest than after mobilization. Three segments showed an unchanged amount of fluid. There was a significant correlation between the presence of intradiscal fluid and the amount of bone marrow edema on MRI and the presence of degenerative endplate abnormalities on CT, respectively. CONCLUSION: The replacement of intradiscal vacuum phenomenon by intradiscal fluid is a time- and position-dependent dynamic process and is related to Modic type 1 degenerative disk disease and degenerative endplate changes.

Surgical therapy of skeletal complications in multiple myeloma.

Patients with multiple myeloma are often treated surgically as though they have bone metastases. Due to major differences in oncological therapy and comparatively long survival times these patients should be considered separately. Seventy-five multiple myeloma patients were treated surgically (83 interventions) for skeletal complications of the disease. Location and dissemination, symptoms, method of surgery, complications, recurrence and survival time were evaluated retrospectively. Most of the lesions were in the axial skeleton or the proximal extremities apart from one distal lesion of the fibula, and most surgery was performed in the spine (35 patients). The mean follow-up of patients was 5.4 years (range 1-25 years). Survival proved to be very favourable (37% at five years). Patients with a single bone lesion, a negative bone marrow biopsy, no paraproteinaemia in serum or a Salmon-Durie-stage I had a better survival probability. Surgical treatment in patients with multiple myeloma was mostly limited to a palliative approach but survival time was better (37% at five years) than in patients with metastatic bone disease which has to be considered in their surgical treatment.

Measuring perfusion and permeability in renal cell carcinoma with dynamic contrast-enhanced MRI: a pilot study.

PURPOSE: To retrospectively assess an improved quantitative methodology with separate assessment of perfusion and permeability for characterization of primary renal cell carcinoma (RCC) and monitoring antiangiogenic treatment. MATERIALS AND METHODS: Fifteen RCC patients before surgery, 6 RCC patients before and after neoadjuvant antiangiogenic therapy, and 15 patients without renal disease underwent dynamic contrast-enhanced (DCE)-MRI of the kidney with integrated retrospective respiratory triggering and an individual arterial input function. Tracer kinetic analysis was performed with a two-compartment-filtration-model for the kidney data and a two-compartment-exchange-model for the tumor data, providing four independent parameters: the perfusion-parameters plasma flow (F(P)) and plasma volume (V(P)), and the permeability-parameters extraction flow (F(E)) and extravascular-extracellular volume (V(E)). RESULTS: In tumors F(P) and F(E) were significantly lower than in normal kidneys. Tracer kinetic analysis displayed hemodynamic alteration caused by vessel infiltration or necrosis. Papillary RCC could be differentiated from clear-cell variants by a distinct perfusion pattern. In antiangiogenically treated RCC V(E) was not significantly decreased, while the perfusion parameters V(P) and F(P) were significantly diminished. CONCLUSION: DCE-MRI with integrated motion compensation enables evaluation of primary RCC and detects distinct perfusion patterns. Quantification with a two-compartment-exchange-model produces a separate perfusion- and permeability characterization and may become a diagnostic tool to monitor antiangiogenic treatment.

Multiparameter MRI assessment of normal-appearing and diseased vertebral bone marrow.

OBJECTIVE: To evaluate spin-lattice (T1) and spin-spin (T2) relaxation times as well as apparent diffusion coefficients (ADCs) of the fat and water components in the vertebral bone marrow (vBM) of patients with benign and malignant lesions. METHODS: Forty-four patients were examined at 1.5 T: there were 24 osteoporotic vertebral fractures (15 women, 9 men; median age: 73, 48-86 years) and 20 malignant vertebral infiltrations (9 women, 11 men; median age: 60, 25-87). Relaxation times were determined separately for the water and the fat component using a saturation-recovery technique for T1 and measurements with variable echo times for T2. ADCs were determined with a diffusion-weighted (DW) echo-planar imaging (EPI) and a single-shot turbo-spin-echo (ssTSE) sequence. RESULTS: T1 of the water component and ADCs were significantly increased in the lesions compared with normal-appearing vBM (malignant: 1,252 vs. 828 ms, osteoporotic: 1,315 vs. 872 ms). ADCs determined with the DW-ssTSE were significantly increased compared with the DW-EPI. ADCs determined with the DW-ssTSE differed significantly between osteoporotic and malignant lesions (1.74 vs 1.35 x 10⁻³ mm²/s. CONCLUSIONS: All parameters exhibit significant differences between normal-appearing vBM and the lesions. However, only the ADCs determined with the DW-ssTSE differed significantly between osteoporotic fractures and malignant lesions, potentially allowing for a differential diagnosis of these two entities.

Whole-body imaging of bone marrow.

For bone marrow screening, multimodality algorithms including conventional radiographs, bone scintigraphy, multislice computed tomography CT (MS-CT) scan, and dedicated magnetic resonance imaging (MRI) are widely established in clinical routine. Although radiographs are used as a basic imaging procedure for clarification of suspected focal bone pathologies, low sensitivity has been reported for the detection of limited osteolytic bone marrow destruction. Therefore, skeletal scintigraphy often is used as a more sensitive and integrated method in patients with suspected malignant bone marrow disease. MS-CT scan is the method of choice in the assessment of bone stability and allows for evaluation of fracture risk. Hybrid imaging concepts, such as positron emission tomography-computed tomography (PET-CT) scan, have been established as an effective tool for the detection of skeletal metastases, using the additional metabolic information of a PET scan for the assessment of tumor viability and therapy response. MRI is an imaging technique that allows direct visualization of bone marrow components with high spatial resolution. The unique soft-tissue contrast of MRI enables precise assessment of bone marrow infiltration before osteolytic changes become visible in MS-CT or metabolic changes occur in bone scintigraphy or a PET scan. Furthermore it can depict tumor expansion into adjacent paraosseous structures, such as the spinal canal. The development of multichannel whole-body MRI (WB-MRI) systems has enabled bone marrow screening without use of ionizing radiation at high diagnostic accuracy. Parallel imaging techniques in combination with global matrix coil concepts, as well as the introduction of high-field whole-body scanners, have substantially reduced acquisition times without compromises in spatial resolution. WB-MRI has successfully been applied for screening of bone metastases and hematologic bone marrow diseases, like multiple myeloma, lymphoma, and histiocytosis X. Furthermore, it has recently been proposed for the assessment of primarily benign bone diseases predisposing for malignancy (e.g., multiple cartilaginous exostoses). This article provides an overview of state-of-art whole-body imaging of the bone marrow and highlights present and potential future applications, especially in the field of WB-MRI.

Comprehensive imaging of tumor recurrence in breast cancer patients using whole-body MRI at 1.5 and 3 T compared to FDG-PET-CT.

PURPOSE: To compare the diagnostic accuracy for the detection of tumor recurrence in breast cancer patients using whole-body-MRI (WB-MRI) at 1.5 or 3T compared to FDG-PET-CT. MATERIALS AND METHODS: Thirty-three female patients with breast cancer and suspicion of recurrence underwent FDG-PET-CT and WB-MRI. Coronal T1w-TSE- and STIR-sequences, HASTE-imaging of the lungs, contrast-enhanced T1w- and T2w-TSE-sequences of the liver, brain and abdomen were performed, using a WB-MRI-scanner at 1.5 (n=23) or 3T (n=10). Presence of local recurrence, lymph node involvement and distant metastatic disease was assessed using clinical and radiological follow-up as a standard of reference. RESULTS: Tumor recurrence was found in 20 of 33 patients. Overall 186 malignant foci were detected with WB-MRI and PET-CT. Both modalities revealed two recurrent tumors of the breast. PET-CT detected more lymph node metastases (n=21) than WB-MRI (n=16). WB-MRI was more precise in the detection of distant metastases (n=154 versus n=147). Sensitivity was 93% (172/186) and 91% (170/186) for WB-MRI and PET-CT, specificity was 86% (66/77) and 90% (69/77), respectively. Examination times for WB-MRI at 1.5 and 3T were 51 and 43 min, respectively, examination time for PET-CT was 103 min. CONCLUSION: WB-MRI and PET-CT are useful for the detection of tumor recurrence in the follow-up of breast cancer. WB-MRI is highly sensitive to distant metastatic disease. PET-CT is more sensitive in detecting lymph node involvement. Tumor screening with WB-MRI is feasible at 1.5 and 3T, scan time is further reduced at 3T with identical resolution.

High-resolution whole-body magnetic resonance imaging applications at 1.5 and 3 Tesla: a comparative study.

OBJECTIVES: To analyze the impact of altered magnetic field properties on image quality and on potential artifacts when an established whole-body magnetic resonance imaging (WB-MRI) protocol at 1.5 Tesla (T) is migrated to 3 T. MATERIALS AND METHODS: Fifteen volunteers underwent noncontrast magnetic resonance imaging (MRI) on 32-channel whole body-scanners at 1.5 and 3 T with the use of parallel acquisition techniques (PAT). Coronal T1-weighted TSE- and short tau inversion recovery (STIR)-sequences at 4 body levels including sagittal imaging of the whole spine were performed. Additional axial HASTE-imaging of lung and abdomen, T1-/T2-weighted-TSE- and EPI-sequences of the brain and T2-weighted respiratory-triggered imaging of the liver was acquired. Both data sets were compared by 2 independent readers in respect to artifacts and image quality using a 5-point scale. Regions of pronounced artifacts were defined. RESULTS: Overall image impression was both qualitatively rated as "good" at 1.5 and 3 T for T1-w-TSE- and STIR-imaging of the whole body and spine. At 1.5 T, significantly better quantitative values for overall image quality were found for WB-STIR, T2-w-TSE imaging of the liver and brain (Wilcoxon Mann-Whitney U Test; P < 0.05), overall rated as good at 3 T. Significantly higher dielectric effects at 3 T were affecting T1-w- and STIR-WB-MRI, and HASTE of the abdomen and better image homogeneity at 1.5 T was observed for T1-weighted-/STIR-WB-MRI and T1-w-TSE-imaging of the spine. Pulsation artifacts were significantly increased at 3 T for T1-w WB-MRI. Significantly higher susceptibility artifacts were found for GRE-sequences of the brain at 3 T. Motion artifacts, Gibbs-Ringing, and image distortion was not significantly different and showed slightly higher quantitative values at 3 T (except for HASTE imaging of the abdomen). Overall scan time was 45 minutes and 44 seconds at 1.5 T and 40 minutes and 28 seconds at 3 T at identical image resolution. CONCLUSION: Three Tesla WB-MRI is feasible with good image quality comparable to 1.5 T. 3.0 T WB-MRI shows significantly more artifacts with a mild to moderate impact on image assessment. Therefore 1.5 T WB-MRI is the preferred image modality. Overall scan time at 3 T is reduced with the use of parallel imaging at a constant image resolution.

Whole-body magnetic resonance imaging and positron emission tomography-computed tomography in oncology.

The advent of positron emission tomography-computed tomography (PET-CT) and whole-body magnetic resonance imaging (WB-MRI) has introduced tumor imaging with a systemic and functional approach compared with established sequential, multimodal diagnostic algorithms.Whole-body PET with [18F]-fluoro-2-desoxy-glucose is a useful imaging procedure for tumor staging and monitoring that can visualize active tumor tissue by detecting pathological glucose metabolism. The combination of PET with the detailed anatomical information of multislice computed tomography as dual-modality scanners has markedly increased lesion localization and diagnostic accuracy compared with both modalities as standalone applications.Hardware innovations, such as the introduction of multi-receiver channel whole-body MRI scanners at 1.5 and, recently, 3 T, combined with acquisition acceleration techniques, have made high-resolution WB-MRI clinically feasible. Now, a dedicated assessment of individual organs with various soft tissue contrast, spatial resolution, and contrast media dynamics can be combined with whole-body anatomical coverage in a multiplanar imaging approach. More flexible protocols (eg, T1-weighted turbo spin-echo and short inversion recovery imaging, dedicated lung imaging or dynamic contrast-enhanced studies of the abdomen) can be performed within 45 minutes.Whole-body magnetic resonance imaging has recently been proposed for tumor screening of asymptomatic individuals, and potentially life-changing diagnoses, such as formerly unknown malignancy, have been reported. However, larger patient cohort studies will have to show the cost efficiency and the clinical effectiveness of such an approach.For initial tumor staging, PET-CT has proved more accurate for the definition of T-stage and lymph node assessment, mainly because of the missing metabolic information in WB-MRI. However, new applications, such as magnetic resonance whole-body diffusion-weighted imaging or lymphotropic contrast agents, may significantly increase sensitivity in near future. Whole-body magnetic resonance imaging has shown advantages for the detection of distant metastatic disease, especially from tumors frequently spreading to the liver or brain and as a whole-body bone marrow screening application. Within this context, WB-MRI is highly accurate for the detection of skeletal metastases and staging of multiple myeloma. This article summarizes recent developments of CT/PET-CT and WB-MRI and highlights their performance within the scope of systemic oncological imaging.

High-resolution whole-body magnetic resonance image tumor staging with the use of parallel imaging versus dual-modality positron emission tomography-computed tomography: experience on a 32-channel system.

OBJECTIVE: The objective of this study was to compare the accuracy in staging of various malignant tumors with whole-body magnetic resonance imaging (WB-MRI) using parallel imaging (PAT) and positron emission tomography-computed tomography (PET-CT). MATERIALS AND METHODS: In a prospective study, 41 patients withoncologic diseases underwent [F]-fluoro-2-deoxy-D-glucose PET-CT for tumor staging and WB-MRI on a 32-channel-scanner with the use of PAT. Coronal T1w and STIR sequences at 5 body levels, axial HASTE imaging of the lung, and contrast-enhanced T1w sequences of the liver, brain, and abdomen were performed. TNM stage was assessed for both modalities in a separate consensus reading using histologic results and radiologic follow up within 6 months as the standard of reference. RESULTS: Three primary and 4 recurrent tumors were detected; one recurrent tumor was missed with WB-MRI. Sixty benign and 60 malignant lymph nodes were detected with a sensitivity of 98% and specificity of 83% for PET-CT and 80%/75% for WB-MRI, respectively. One hundred ninety-one malignant and 77 benign distant lesions were detected with a sensitivity/specificity of 82% for PET-CT and 96%/82% for WB-MRI. Accuracy for correct TNM staging was 96% for PET-CT and 91% for WB-MRI. CONCLUSION: WB-MRI and PET-CT are reliable imaging modalities for tumor staging. WB-MRI is highly sensitive in detecting distant metastases; PET-CT is superior in lymph node staging. PAT makes high-resolution WB-MRI feasible within less than 1 hour.

The role of 68Ga-DOTATATE PET/CT in suspected neuroendocrine tumors.

UNLABELLED: In patients with suspected but yet not localized neuroendocrine tumors (NETs), early diagnosis or reliable exclusion is crucial for optimal individual prognosis and therapy. Despite recourse to several imaging modalities, the definite diagnosis of NET can be challenging. Therefore, we tested (68)Ga-DOTATATE PET/CT as a tool for improved diagnosis in a cohort of patients with suspected, nonlocalized NET. METHODS: (68)Ga-DOTATATE PET/CT recordings were obtained in 104 consecutive patients meeting at least one of the following criteria: clinical suspicion of NET (n = 70), elevated blood levels of tumor markers (n = 49), and image-based suspicion of NET (n = 53). The presence of NET was validated by histopathology (n = 49) or clinical follow-up of 107 ± 59 wk (n = 55). RESULTS: In 36 of 104 patients (35%), NET was histologically verified, most frequently located in the small bowel (10/36), pancreas (8/36), lung (5/36), and stomach (2/36). Twelve patients had tumors of nonneuroendocrine origin, and 7 patients had benign tumors. (68)Ga-DOTATATE PET/CT identified NET in 29 of the 36 cases and excluded the presence of a NET in 61 of the 68 non-NET patients, indicating a sensitivity of 81% and specificity of 90%. The PET/CT gave a false-positive result in 7 patients and a false-negative in another 7 patients, indicating positive and negative predictive values of 81% and 90%, respectively, and an accuracy of 87%. Chromogranin A levels were significantly higher in both PET-positive patients (1,841 vs. 342 ng/mL; P < 0.05) and patients with verified NET (2,214 vs. 524 ng/mL; P < 0.05). CONCLUSION: In patients with suspected NETs due to clinical symptoms, elevated levels of tumor markers, or indeterminate tumors suggestive of NET, (68)Ga-DOTATATE PET/CT is highly accurate, thus supporting its use in clinical routine diagnostics.

Radioembolization of symptomatic, unresectable neuroendocrine hepatic metastases using yttrium-90 microspheres.

PURPOSE: To evaluate safety, efficacy, and symptom-control of radioembolization in patients with unresectable liver metastases from neuroendocrine tumors (NETLMs). MATERIALS AND METHODS: Forty-two patients (mean age of 62 years) with treatment-refractory NETLMs underwent radioembolization using yttrium-90 ((90)Y) resin microspheres. Posttreatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST) and tumor-marker levels. Laboratory and clinical toxicities and clinical symptoms were monitored. RESULTS: The median activity delivered was 1.63 GBq (range 0.63-2.36). Imaging follow-up using RECIST at 3-month follow-up demonstrated partial response, stable disease, and progressive disease in 22.5, 75.0, and 2.5% of patients, respectively. In 97.5% of patients, the liver lesions appeared hypovascular or partially necrotic. The mean follow-up was 16.2 months with 40 patients (95.2%) remaining alive. The median decrease in tumor-marker levels at 3 months was 54.8% (chromogranin A) and 37.3% (serotonin), respectively. There were no acute or delayed toxicities greater than grade 2 according to Common Terminology Criteria for Adverse Events [CTCAE (v3.0)]. No radiation-induced liver disease was noted. Improvement of clinical symptoms 3 months after treatment was observed in 36 of 38 symptomatic patients. CONCLUSION: Radioembolization with (90)Y-microspheres is a safe and effective treatment option in patients with otherwise treatment-refractory NETLMs. Antitumoral effect is supported by good local tumor control, decreased tumor-marker levels, and improved clinical symptoms. Further investigation is warranted to define the role of radioembolization in the treatment paradigm for NETLMs.

Quantitative analysis of the diffusion-weighted steady-state free precession signal in vertebral bone marrow lesions.

OBJECTIVES: : Diffusion-weighted steady-state free precession (DW-SSFP) sequences have shown great potential for the differential diagnosis of benign osteoporotic and malignant neoplastic vertebral compression fractures, which appear hypo- to isointense or hyperintense in DW-SSFP magnetic resonance imaging, respectively. In contrast to other diffusion weighting sequences, the DW-SSFP signal depends not only on the apparent diffusion coefficient (ADC), but also on the tissue relaxation times and sequence parameters. The purpose of the present study was to provide a detailed analysis of the DW-SSFP signal in benign and malignant vertebral lesions (VLs) and in vertebral bone marrow (VBM) to understand the observed signal alterations and their dependence on tissue and sequence parameters. MATERIALS AND METHODS: : Magnetic resonance imaging was performed in 40 patients with benign (n = 20) or malignant (n = 20) VLs to determine the fat fraction and tissue parameters (ADC, T1, T2, T2*) for both the water and fat signal. With these values, the DW-SSFP signal was simulated and compared with the measured signals for different diffusion gradients by determining the signal intensity ratio between the SSFP signals of the lesions and of normal-appearing VBM for both malignant and benign VLs. RESULTS: : The simulated DW-SSFP contrast agreed well with the measured contrast and provided a very good differentiation between benign osteoporotic and malignant VLs. ADCs were significantly different in both lesion types (malignant 1.36 vs. osteoporotic 1.77 × 10 mm/s); however, the observed contrast differences were caused predominantly by an opposed-phase readout in combination with significantly different T2* values (malignant 22 vs. osteoporotic 14 ms) and fat fractions (malignant 3.9% vs. osteoporotic 12%) in the lesions as well as significantly different fat fractions in normal-appearing VBM (malignant 42% vs. osteoporotic 52%) of both patient groups. CONCLUSIONS: : Although the ADCs of the evaluated malignant and benign VLs showed highly significant differences, the influence of diffusion on the DW-SSFP signal contrast is relatively low compared with other tissue parameters due to the very complex signal mechanism of the SSFP sequence. Thus, the observed DW-SSFP signal contrast of different VLs (hypo-/isointense vs. hyperintense signal) is rather fat- and T2*-weighted than diffusion-weighted. The intermediate diffusion weighting of the applied SSFP sequence, however, helps to shift the different contrasts into a signal range that is easily visually accessible.

Treatment with octreotide does not reduce tumor uptake of (68)Ga-DOTATATE as measured by PET/CT in patients with neuroendocrine tumors.

UNLABELLED: We hypothesized that (68)Ga-DOTATATE uptake of neuroendocrine tumors is sensitive to therapy with a nonradioactive somatostatin analog. METHODS: (68)Ga-DOTATATE PET/CT was used to examine 105 patients, 35 of whom had been pretreated with long-acting octreotide. The maximum standardized uptake value (SUV(max)) of target tissues, as well as metastases, was compared between the groups of patients with (group 1) and without (group 2) octreotide treatment. RESULTS: The SUV(max) of the spleen and liver was significantly lower in group 1 than in group 2 (both P < 0.001). There were no significant group differences in SUV(max) for primary tumors (28.6 ± 6.8 vs. 32.9 ± 31.5) or metastases in the liver (27.2 ± 14.8 vs. 25.7 ± 10.7), lymph nodes (41.4 ± 19.5 vs. 25.0 ± 6.3), or skeleton (39.5 ± 22.0 vs. 15.4 ± 7.8). In 9 patients available for intraindividual comparison, tumor uptake was unaffected by treatment with somatostatin analogs (21.7 vs. 20.6; P = 0.93). CONCLUSION: Treatment with a long-acting somatostatin analog did not significantly reduce (68)Ga-DOTATATE binding in neuroendocrine tumors but tended to improve the tumor-to-background ratio.

68Ga-DOTATATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differentiated neuroendocrine tumors.

UNLABELLED: We aimed to evaluate (68)Ga-DOTATATE PET/CT for the early prediction of time to progression and clinical outcome after a first cycle of peptide receptor radionuclide treatment (PRRT) in a cohort of patients with well-differentiated neuroendocrine tumors. METHODS: Thirty-three consecutive patients (22 men and 11 women; mean age +/- SD, 57.8 +/- 12.1 y) were investigated at baseline and again 3 mo after initiation of the first cycle of PRRT. (68)Ga-DOTATATE receptor expression was assessed using 2 measures of standardized uptake value (SUV): maximum SUV (SUV(max)) and tumor-to-spleen SUV ratio (SUV(T/S)). Percentage change in SUV scores after PRRT relative to baseline (DeltaSUV) was calculated. After completing 1-3 cycles of PRRT, patients entered the follow-up study, for estimation of time to progression. According to the Response Evaluation Criteria in Solid Tumors, progression was defined on the basis of contrast-enhanced CT. Clinical symptoms, as well as the tumor markers chromogranin A and neuron-specific enolase, were also recorded during regular follow-up visits. RESULTS: The 23 of 31 patients with decreased SUV(T/S) after the first PRRT cycle had longer progression-free survival than did the 8 of 31 patients with stable or increased scores (median survival not reached vs. 6 mo, P = 0.002). For the 18 of 33 patients showing a reduction in SUV(max), there was no significant difference in progression-free survival (median survival not reached vs. 14 mo, P = 0.22). Multivariate regression analysis identified SUV(T/S) as the only independent predictor for tumor progression during follow-up. In the 17 of 33 patients with clinical symptoms before PRRT, DeltaSUV(T/S) correlated with clinical improvement (r = 0.52, P < 0.05), whereas DeltaSUV(max) did not (r = 0.42, P = 0.10). Changes in the tumor markers (chromogranin A and neuron-specific enolase) did not predict DeltaSUV scores, clinical improvement, or time to progression. CONCLUSION: Decreased (68)Ga-DOTATATE uptake in tumors after the first cycle of PRRT predicted time to progression and correlated with an improvement in clinical symptoms among patients with well-differentiated neuroendocrine tumors; DeltaSUV(T/S) was superior to DeltaSUV(max) for prediction of outcome.

Whole-body MRI for the staging and follow-up of patients with metastasis.

The advent of whole-body MRI (WB-MRI) has introduced tumor imaging with a systemic approach compared to established sequential, multi-modal diagnostic algorithms. Hardware innovations, such as the introduction of multi-receiver channel whole-body scanners at 1.5 T and recently 3T, combined with acquisition acceleration techniques, have made high resolution WB-MRI clinically feasible. Now, a dedicated assessment of individual organs with various soft tissue contrast, spatial resolution and contrast media dynamics can be combined with whole-body anatomic coverage in a multi-planar imaging approach. More flexible protocols, e.g. including T1-weighted TSE- and STIR-imaging, dedicated lung imaging or dynamic contrast-enhanced studies of the abdomen can be performed within less than 45 min. For initial tumor staging PET-CT as a competing whole-body modality in oncologic imaging has proved more accurate for the definition of T-stage and lymph node assessment, using the additional metabolic information of PET for the assessment of tumor viability and therapy response. However, new applications, such as MR-whole-body diffusion imaging, may significantly increase sensitivity in near future. WB-MRI has shown advantages for the detection of distant metastatic disease, especially from tumors frequently spreading to the liver or brain and it is especially useful as a radiation-free alternative for the surveillance of tumor patients with multiple follow-up exams. Furthermore, it has been introduced as a whole-body bone marrow screening application. Within this context WB-MRI is highly accurate for the detection of skeletal metastases and staging of hematologic diseases, such as multiple myeloma or lymphoma. This article summarizes recent developments and applications of WB-MRI and highlights its performance within the scope of systemic oncologic staging and surveillance.

Assessment of the internal craniocervical ligaments with a new magnetic resonance imaging sequence: three-dimensional turbo spin echo with variable flip-angle distribution (SPACE).

PURPOSE: Lesions close to the internal craniocervical ligaments are a common problem in patients with whiplash injuries. The aim of this study was to evaluate the morphology and visibility of these ligamentous structures with a new isotropic three-dimensional (3D) turbo-spin-echo (TSE) technique. MATERIALS AND METHODS: MR (MR) images of the cervical spine of 52 healthy subjects (27 women and 25 men; mean age=29 years; age range=18-40 years) were taken with a T2-weighted 3D TSE sequence with variable flip-angle distribution [SPACE (Sampling Perfection with Application optimized Contrasts using different flip-angle Evolution)] at 1.5 T (Magnetom Avanto, Siemens Erlangen, Germany). Two experienced musculoskeletal radiologists read the images independently on a 3D imaging and postprocessing workstation. The visibility and morphology of the alar ligaments were evaluated on a five-point scale, and inter-reader correlation was assessed with kappa statistics. RESULTS: Both alar ligaments were detected in all subjects. Twenty-eight (53.8%) of the alar ligaments could not be seen within one slice of the standard coronal imaging plane but could adequately be visualized in an oblique reconstruction adapted to the orientation of the ligaments on the axial slices. Inter-reader correlation for visibility on MR imaging (MRI) of the internal craniocervical ligaments was high (left+right side, kappa=0.95). Most (94%) alar ligaments presented symmetrically. In the axial plane, 60% were oriented neutral and 40% had a backward orientation. In the coronal plane, 67% were oriented caudocranially and 33% were oriented horizontally. The shape of the ligaments was parallel in half and was V-shaped in the other half. The alar ligaments had homogeneous low-signal intensity in 56% and heterogeneous low-signal intensity in 44%. The apical ligament of the dens was seen (excellent-good-moderate) in 61% (reader 1) and 52% (reader 2). The tectorial membranes and the transverse ligament of the atlas were shown (excellent-good) in all subjects. CONCLUSIONS: MRI with acquisition of an isotropic SPACE technique allows high-resolution imaging of the craniocervical ligaments in all orientations. Reconstruction of the image data in the variable orientation of the alar ligaments allowed for excellent depiction within one slice such that partial volume artifacts that hamper image analysis can be eliminated.