Reference values of physiological 18F-FET uptake: Implications for brain tumor discrimination.

PURPOSE: The aim of this study was to derive reference values of 18F-fluoro-ethyl-L-tyrosine positron emission tomography (18F-FET-PET) uptake in normal brain and head structures to allow for differentiation from tumor tissue. MATERIALS AND METHODS: We examined the datasets of 70 patients (median age 53 years, range 15-79), whose dynamic 18F-FET-PET was acquired between January 2016 and October 2017. Maximum standardized uptake value (SUVmax), target-to-background standardized uptake value ratio (TBR), and time activity curve (TAC) of the 18F-FET-PET were assessed in tumor tissue and in eight normal anatomic structures and compared using the t-test and Mann-Whitney U-test. Correlation analyses were performed using Pearson or Spearman coefficients, and comparisons between several variables with Pearson's chi-squared tests and Kruskal-Wallis tests as well as the Benjamini-Hochberg correction. RESULTS: All analyzed structures showed an 18F-FET uptake higher than background (threshold: TBR > 1.5). The venous sinuses and cranial muscles exhibited a TBR of 2.03±0.46 (confidence interval (CI) 1.92-2.14), higher than the uptake of caudate nucleus, pineal gland, putamen, and thalamus (TBR 1.42±0.17, CI 1.38-1.47). SUVmax, TBR, and TAC showed no difference in the analyzed structures between subjects with high-grade gliomas and subjects with low-grade gliomas, except the SUVmax of the pineal gland (t-tests of the pineal gland: SUVmax: p = 0.022; TBR: p = 0.411). No significant differences were found for gender and age. CONCLUSION: Normal brain tissue demonstrates increased 18F-FET uptake compared to background tissue. Two distinct clusters have been identified, comprising venous structures and gray matter with a reference uptake of up to SUVmax of 2.99 and 2.33, respectively.

Outcome after Discontinuing Long-Term Benzimidazole Treatment in 11 Patients with Non-resectable Alveolar Echinococcosis with Negative FDG-PET/CT and Anti-EmII/3-10 Serology.

BACKGROUND/AIMS: Benzimidazoles are efficacious for treating non-resectable alveolar echinococcosis (AE), but their long-term parasitocidal (curative) effect is disputed. In this study, we prospectively analyzed the potential parasitocidal effect of benzimidazoles and whether normalization of FDG-PET/CT scans and anti-Emll/3-10-antibody levels could act as reliable "in vivo" parameters of AE-inactivation permitting to abrogate chemotherapy with a low risk for AE-recurrence. METHOD: This prospective study included 34 patients with non-resectable AE subdivided into group A (n = 11), followed-up after diagnosis and begin of chemotherapy at months 6, 12 and 24, and group B (n = 23) with a medium duration of chemotherapy of 10 (range 2-25) years. All patients were assessed by FDG-PET/CT examinations and anti-EmII/3-10 serology. Chemotherapy was abrogated in patients with normalization of FDG-PET/CT and serum anti-EmII/3-10 levels. These patients were closely followed-up for AE recurrence. Endpoint (parasitocidal efficacy) was defined by the absence of AE-recurrence >24 months after stopping treatment. RESULTS: Normalization of FDG-PET/CT scan and anti-EmII/3-10 levels occurred in 11 of 34 patients (32%). After abrogation of chemotherapy in these 11 patients, there was no evidence of AE-recurrence within a median of 70.5 (range 16-82) months. However, the patients' immunocompetence appears pivotal for the described long-term parasitocidal effect of benzimidazoles. CONCLUSIONS: The combination of negative FDG-PET/CT-scans and anti-EmII/3-10 antibody levels seem to be reliable parameters for assessing in vivo AE-larval inactivity after long-term benzimidazole chemotherapy. TRIAL REGISTRATION: clinicaltrials.gov: NCT00658294.

High bone turnover assessed by 18F-fluoride PET/CT in the spine and sacroiliac joints of patients with ankylosing spondylitis: comparison with inflammatory lesions detected by whole body MRI.

BACKGROUND: This study compares the frequency and distribution of increased activity on 18 F-fluoride PET/CT with the presence of bone marrow edema on whole-body MR imaging in the spine and sacroiliac joints (SIJ) of patients with active ankylosing spondylitis (AS). METHODS: Ten patients (6 men and 4 women), between 30 and 58 years old (median 44) with active AS, were prospectively examined with both whole-body MRI and 18 F-fluoride PET/CT. Patients fulfilled modified NY criteria and had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of at least 4. Increased radiotracer uptake in PET/CT and bone marrow edema in whole-body MRI of spine and SIJ was evaluated independently by two blinded observers for each modality. Kappa statistics were used to compare interobserver agreement as well as scores of consensus reading of the two imaging modalities. RESULTS: Analysis of interobserver agreement for PET/CT yielded a kappa value of 0.68 for spinal lesions and of 0.88 for SIJ lesions. The corresponding kappa values for the MRI modality were 0.64 and 0.93, respectively. More spinal lesions were detected by MRI in comparison to PET/CT (68 vs. 38), whereas a similar number of SIJ quadrants scored positive in both modalities (19 vs. 17). Analysis of agreement of lesion detection between both imaging modalities yielded a kappa value of only 0.25 for spinal lesions and of 0.64 for SIJ lesions. CONCLUSION: Increased 18 F-fluoride uptake in PET/CT is only modestly associated with bone marrow edema on MRI in the spine and SIJ of patients with AS, suggesting different aspects of bone involvement in AS.

Assessment of successful incorporation of cages after cervical or lumbar intercorporal fusion with [(18)F]fluoride positron-emission tomography/computed tomography.

The purpose of this study is to assess the successful incorporation of cages in patients after cervical or lumbar intercorporal fusion with positron-emission tomography/computed tomography (PET/CT). Twenty patients (14 female and 6 male; mean age 58 years, age range 38-73 years) with 30 cervical (n = 13) or lumbar (n = 17) intercorporal fusions were prospectively enrolled in this study. Time interval between last intercorporal intervention and PET/CT ranged from 2 to 116 months (mean 63; median 77 months). IRB approval was obtained for all patients, and written informed consent was obtained from all patients. About 30 min prior to PET/CT scanning, 97-217 MBq (mean 161 MBq) 18F-fluoride were administered intravenously. Patients were imaged in supine position on a combined PET/CT system (Discovery RX/STE, 16/64 slice CT, GE Healthcare). 3D-PET emission data were acquired for 1.5 and 2 min/bed position, respectively, and reconstructed by a fully 3D iterative algorithm (VUE Point HD) using low-dose CT data for attenuation correction. A dedicated diagnostic thin-slice CT was optionally acquired covering the fused region. Areas of increased 18F-fluoride uptake around cages were determined by one double-board certified radiologist/nuclear physician and one board certified radiologist in consensus. In 12/20 (60%) patients, increased 18F-fluoride uptake around cages was observed. Of the 30 intercorporal fusions, 15 (50%) showed increased 18F-fluoride uptake. Median time between intervention and PET/CT examination in cages with increased uptake was 37 months (2-116 months), median time between intervention and PET/CT examination in those cages without increased uptake was 91 months (19-112 months), p (Wilcoxon) = 0.01 (one-sided). 14/29 (48%) cages with a time interval > 1 year between intervention and PET/CT scan showed an increased uptake. In conclusion, PET/CT frequently shows increased 18F-fluoride uptake in cervical and lumbar cages older than 1 year (up to almost 8 years in cervical cages and 10 years in lumbar cages) possibly indicating unsuccessful fusion due to increased stress/microinstability.

18F-FET PET/CT in advanced head and neck squamous cell carcinoma: an intra-individual comparison with 18F-FDG PET/CT.

PURPOSE: To assess the diagnostic value of O-2-fluoro-18(F)-ethyl-L-tyrosine ((18)F-FET) positron emission tomography/computed tomography (PET/CT) for patients with advanced head and neck squamous cell carcinoma compared with 18F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/CT at initial staging and following radiochemotherapy. PROCEDURES: Thirteen patients were prospectively enrolled; each of them underwent an (18)F-FDG PET/CT and (18)F-FET PET/CT before treatment. Ten of those were scanned 10 weeks after treatment. RESULTS: Sensitivity, specificity, and accuracy for (18)F-FDG PET/CT (primary and lymph node metastases) at initial staging were 89%, 50%, and 81%. For (18)F-FET PET/CT the numbers were 70%, 90%, and 74%. Sensitivity, specificity, and accuracy for (18)F-FDG PET/CT at follow-up were 71%, 65%, and 67%. For (18)F-FET PET/CT the numbers were 29%, 100%, and 83%. Additionally, (18)F-FDG PET/CT detected a higher number of second malignancies or distant metastases. CONCLUSIONS: (18)F-FET is no substitute for (18)F-FDG. Although it is more specific, too many malignant lesions are missed due to its lower sensitivity.

18F-fluoride PET/CT for detection of sacroiliitis in ankylosing spondylitis.

PURPOSE: The aim of this study was to evaluate the performance of (18)F-fluoride-PET/CT (PET/CT) for the diagnosis of sacroiliac joint (SIJ) arthritis in patients with active ankylosing spondylitis (AS). METHODS: Included in the study were 15 patients with AS according to the modified New York criteria (AS group) and with active disease and 13 patients with mechanical low back pain (MLBP; control group) who were investigated with whole-body (18)F-fluoride PET/CT. The ratio of the uptake in the SIJ and that in the sacrum (SIJ/S) was calculated for every joint. RESULTS: The mean SIJ/S ratio of 30 quantified joints in the AS group was 1.66 (range 1.10-3.07) with PET/CT, and the mean SIJ/S ratio of 26 quantified joints in the MLBP group was 1.12 (range 0.71-1.52). The area under the receiver operating characteristic curve for SIJ arthritis was 0.84. With plain radiography as a the gold standard and taking an SIJ/S ratio of >1.3 as the threshold, the sensitivity, specificity and accuracy on a per patient basis were 80%, 77% and 79%, respectively. On a per SIJ basis, the greatest sensitivity (94%) was found in grade 3 sacroiliitis (n = 16). CONCLUSION: Our results suggest that quantitative (18)F-fluoride PET/CT may play a role in the diagnosis of sacroiliitis in active AS and is an alternative to conventional bone scintigraphy in times of molybdenum shortage.

The performance of computer-aided detection when analyzing prior mammograms of newly detected breast cancers with special focus on the time interval from initial imaging to detection.

PURPOSE: The clinical role of CAD systems to detect breast cancer, which have not been on cancer containing mammograms not detected by the radiologist was proven retrospectively. METHODS: All patients from 1992 to 2005 with a histologically verified malignant breast lesion and a mammogram at our department, were analyzed in retrospect focussing on the time of detection of the malignant lesion. All prior mammograms were analyzed by CAD (CADx, USA). The resulting CAD printout was matched with the cancer containing images yielding to the radiological diagnosis of breast cancer. CAD performance, sensitivity as well as the association of CAD and radiological features were analyzed. RESULTS: 278 mammograms fulfilled the inclusion criteria. 111 cases showed a retrospectively visible lesion (71 masses, 23 single microcalcification clusters, 16 masses with microcalcifications, in one case two microcalcification clusters). 54/87 masses and 34/41 microcalcifications were detected by CAD. Detection rates varied from 9/20 (ACR 1) to 5/7 (ACR 4) (45% vs. 71%). The detection of microcalcifications was not influenced by breast tissue density. CONCLUSION: CAD might be useful in an earlier detection of subtle breast cancer cases, which might remain otherwise undetected.

The adjacent vessel on dynamic contrast-enhanced breast MRI.

OBJECTIVE: The purpose of this study was to investigate whether an adjacent vessel leading to an enhancing lesion seen on subtraction images can help differentiate malignant from benign breast lesions and therefore increase the specificity of breast MRI. MATERIALS AND METHODS: The study included 132 histologically verified lesions (71 malignant lesions, 10 pure carcinoma in situ, and 51 benign lesions) enhancing on dynamic breast MRI before biopsy. The lesions were evaluated by three radiologists in a double-blinded manner. The presence of an adjacent vessel was supposed if at least two observers voted positively. RESULTS: Sixty-one (85.9%) of 71 malignant lesions, six (60%) of 10 carcinomas in situ, and 10 (19.6%) of 51 benign lesions were associated with an adjacent vessel, which differed significantly (p < 0.001) between benign and malignant lesions (the latter with and without including pure carcinoma in situ), leading to a positive predictive value of 85.9% (87% including pure carcinomas in situ), a negative predictive value of 80.4% (74.5% including pure carcinomas in situ), an accuracy of 83.2% (81.6% including pure carcinomas in situ), a sensitivity of 85.9% (82.7% including carcinomas in situ), and a specificity of 80.4% for this sign concerning malignancy. CONCLUSION: The presence of an adjacent vessel seen on subtraction images promises to be a good marker for malignancy and can therefore help increase the specificity of breast MRI.

CAD for mammography: the technique, results, current role and further developments.

CAD systems, developed to assist the radiologist in the detection of suspicious lesions on mammograms, are currently controversially discussed. The highly sensitive detection of malignant structures including priors by CAD is linked with a low specific performance and a high rate of falsely positive markings. This causes controversial results regarding the effect of CAD systems for the diagnosing radiologist. This review aims to give an overview of the current literature, to state the currently discussed controversial results of CAD and to give an outlook on the next developments, which are not limited to senology, but include many other applications of CAD systems in radiology.

Differentiation of phyllodes breast tumors from fibroadenomas on MRI.

OBJECTIVE: The purpose of our study was to evaluate the MRI appearance of phyllodes breast tumors and to differentiate them from fibroadenomas. MATERIALS AND METHODS: MR images were obtained on a 1.5-T imager. T1- and T2-weighted sequences and dynamic 2D fast-field echo T1-weighted sequences were performed. MR images of 23 patients with 24 phyllodes breast tumors (one malignant, 23 benign) were analyzed with respect to morphology and contrast enhancement. The tumors were compared with the MRI appearance of 81 fibroadenomas of 75 patients. RESULTS: Well-defined margins were seen in 87.5% of the phyllodes tumors and 70.4% of the fibroadenomas, and a round or lobulated shape in 100% and 90.1%, respectively. A heterogeneous internal structure was observed in 70.8% of phyllodes tumors and in 49.4% of fibroadenomas. Nonenhancing internal septations were found in 45.8% of phyllodes tumors and 27.2% of fibroadenomas. A significantly greater increase in signal was seen on T2-weighted images in the tissue surrounding phyllodes tumors (21%) compared with fibroadenomas (1.2%). Most of both lesions appeared with low signal intensity on T1- and T2-weighted images. After the administration of contrast material, 33.3% of phyllodes tumors and 22.2% of fibroadenomas showed a suspicious signal intensity-time course. CONCLUSION: Phyllodes breast tumors and other fibroadenomas cannot be precisely differentiated on breast MRI. Phyllodes tumors have benign morphologic features and contrast enhancement characteristics suggestive of malignancy in 33% of cases.

Potential MRI interpretation model: differentiation of benign from malignant breast masses.

OBJECTIVE: Our objective was to increase the accuracy of breast MRI using a semiquantitative analysis of typical MRI features and their diagnostic potential. The prevalence of recently reported MRI signs of breast lesions were analyzed and compared with other well-known signs. CONCLUSION: New MRI features, especially from T2-weighted images, are promising for more reliable and accurate interpretation of breast lesions. Prospective studies of these findings are required to define cut-off values and test clinical practicality.

Further signs in the evaluation of magnetic resonance mammography: a retrospective study.

PURPOSE: To increase accuracy and reliability of magnetic resonance breast imaging, a new evaluation method might be helpful. The recently suggested evaluation method (Fischer U, et al) resulted in a relevant number of equivocal cases (3 or 4 points). Additional morphologic and dynamic signs as an extension of this score were evaluated. METHOD AND MATERIALS: One hundred thirty-two histologically verified lesions were evaluated by 3 radiologists double-blinded using 2 evaluation methods: 1) method 1 (according to Fischer, et al): 2pt: initial signal increase >100%, washout, centripetal enhancement, 1pt: initial signal increase 50-100%, plateau phenomenon, centrifugal inhomogeneous enhancement, irregular borders, linear, stellar or dendritic structure; and 2) method 2 (according to Malich, et al): 3pt: hook sign (sign of pectoral invasion), 2pt: unifocal edema, blooming. 1pt: hypointensity in T2, lymph nodes >10 mm, skin thickening, adjacent vessels, a lesion's distorted inner architecture, disruption of the mamillary edge; -1pt: isointensity in T2, no edema, enhancing septations; -3pt: hyperintensity in T2, non enhancing septations. Method 1 judged a lesion to be malignant if 5 or more points were given and benign if 2 or less points were given, respectively. Method 2 (mean value of 3 radiologists) was tested in those cases in which a clear possible decision using method 1 was not sufficiently possible. RESULTS: Method 1 alone resulted in a negative predictive value of 96.8% and a positive predictive value of 90.8% (without carcinoma in situ), a sensitivity of 83.1%, a specificity of 58.8%, and revealed uncertain results (3 and 4 points) in 29 cases (out of 132; 22%). Adding the new scoring system in these 29 equivocal cases and an increase of 2 or more points by using method 2 is supposed to be a sign of malignancy; findings suggest a sensitivity of 90.9% and a specificity of 60% if an increase of maximum 1 is observed in benign lesions. In conclusion, our results show that Göttingen score alone has a sensitivity of 83.1%, a specificity of 58.8%; the second evaluation method reveals a sensitivity of 90.9% and a specificity of 60% in equivocal cases of Göttingen score. Göttingen score then reaches in all cases and second, adding the second evaluation method in equivocal cases, a sensitivity of 97% and a specificity of 76.5%. CONCLUSION: The application of a second evaluation method in those cases remaining unclear in Göttingen score can lead to a decrease of uncertainty and a higher sensitivity and specificity of diagnosis in MR mammography. In this study, Göttingen score reaches a sensitivity of 83.1% and a specificity of 58.8%, increasing to a sensitivity of 97% and a specificity of 76.5% when being extended by a second evaluation method in unclear cases.

Effect of breast density on computer aided detection.

PURPOSE: This study was conducted to assess the clinical impact of breast density and density of the lesion's background on the performance of a computer-aided detection (CAD) system in the detection of breast masses (MA) and microcalcifications (MC). MATERIALS AND METHODS: A total of 200 screening mammograms interpreted as BI-RADS 1 and suspicious mammograms of 150 patients having a histologically verified malignancy from 1992 to 2000 were selected by using a sampler of tumor cases. Excluding those cases having more than one lesion or a contralateral malignancy attributable to statistical reasons, 127 cases with 127 malignant findings were analyzed with a CAD system (Second Look 5.0, CADx Systems, Inc., Beavercreek, OH). Of the 127 malignant lesions, 56 presented as MC and 101 presented as MA, including 30 cases with both malignant signs. Overall breast density of the mammogram and density of the lesion's background were determined by two observers in congruence (density a: entirely fatty, density b: scattered fibroglandular tissue, density c: heterogeneously dense, density d: extremely dense). RESULTS: Within the unsuspicious group, 100/200 cases did not have any CAD MA marks and were therefore truly negative (specificity 50%), and 151/200 cases did not have any CAD MC marks (specificity 75.5%). For these 200 cases, the numbers of marks per image were 0.41 and 0.37 (density a), 0.38 and 0.97 (density b), 0.44 and 0.91 (density c), and 0.58 and 0.68 (density d) for MC and MA marks, respectively (Fisher's t-test: n.s. for MC, p < 0.05 for MA). Malignant lesions were correctly detected in at least one view by the CAD system for 52/56 (92.8%) MC and 91/101 (90.1%) MA. Detection rate versus breast density was: 4/6 (66.7%) and 18/19 (94.7%) (density a), 32/33 (97.0%) and 49/51 (96.1%) (density b), 14/15 (93.3%) and 23/28 (82.1%) (density c), and 2/2 (100%) and 1/3 (33.3%) (density d) for MC and MA, respectively. Detection rate versus the lesion's background was: 19/21 (90.5%) and 36/38 (94.7%) (density a), 34/36 (94.4%) and 59/62 (95.2%) (density b), 8/9 (88.9%) and 20/24 (83.3%) (density c), and 9/10 (90%) and 4/8 (50%) (density d) for groups 2 and 3, respectively. Detection rates differed significantly for masses in heterogeneously dense and extremely dense tissue (overall or lesion's background) versus all other densities (Fisher's t-test: p < 0.05). A significantly lowered FP rate for masses was found on mammograms of entirely fatty tissue. CONCLUSION: Overall breast density and density at a lesion's background do not appear to have a significant effect on CAD sensitivity or specificity for MC. CAD sensitivity for MA may be lowered in cases with heterogeneously and extremely dense breasts, and CAD specificity for MA is highest in cases with extremely fatty breasts. The effects of overall breast density and density of a lesion's background appear to be similar.

Application of an exogenous hyperoxic contrast agent in MR mammography: initial results.

There is interest in applying novel methods to dynamic MR mammography (MRM). One such possibility is to administer an exogenous hyperoxic contrast agent, such as carbogen (95-98% O2 and 2-5% CO2) or pure oxygen (100% O2). We report our first experiences with these agents in a patient with an invasive lobular carcinoma. Fourteen dynamic series were acquired with an rf-spoiled 2D multislice gradient echo sequence, including three measurements while breathing air, four measurements with 100% oxygen, three measurements with air and four measurements with carbogen. Afterwards, 0.1 mmol/kg bw of Gd-DTPA was administered to obtain dynamic T1-weighted double-echo 3D axial gradient echo images (TR/TE1/TE2/alpha=7.8 ms/2 ms/4.76 ms/15 degrees) every 90 s up to 4.5 min after injection. The lesion was well delineated on the contrast-enhanced images, contrary to magnitude images reconstructed from the raw data sets acquired during air/oxygen/carbogen breathing. A ROI-based median-filtered signal-time course revealed a tumor signal increase of roughly 15% between scans acquired during air and oxygen breathing. Though preliminary, these first results are encouraging concerning the exploration of these alternative contrast agents in MRM in greater detail.