Nils Schreiter

Evaluation of the potential of PET-MRI fusion for detection of liver metastases in patients with neuroendocrine tumours

AbstractObjectivesThis study was performed to assess the role of retrospective PET-MRI fusion with Ga-68-DOTA(0)-Phe(1)-Tyr(3)-octreotide (Ga-68-DOTATOC) PET and Gd-EOB-DTPA MRI in the detection of hepatic metastases from neuroendocrine tumours (NET).MethodsTwenty-two consecutive patients with suspected liver metastases from histopathologically proven NET were examined with Gd-EOB-DTPA MRI and multiphase contrast-enhanced Ga-68-DOTATOC PET/CT. PET and MRI images were retrospectively fused using commercially available software. Two physicians experienced in nuclear medicine and radiology analysed the images to assess diagnostic confidence and characterise liver lesions.ResultsA total of 181 lesions were detected. PET-MRI showed a sensitivity of 91.2% (significantly superior to PET/CT; P < 0.05) and a specificity of 95.6% (significantly superior to MRI; P < 0.05). PET/CT had a sensitivity of 73.5% and a specificity of 88.2%. MRI had a sensitivity of 87.6% and a specificity of 86.8%. The area under the curve was 0.98 for PET-MRI, 0.96 for MRI, and 0.89 for PET/CT (P < 0.05).ConclusionsRetrospectively fused PET-MRI was superior to multiphase contrast-enhanced Ga-68-DOTATOC PET/CT and Gd-EOB-DTPA MRI in the detection of NET liver metastases. It was more sensitive than PET/CT and more specific than MRI. Fused PET-MRI therefore seems well suited for surgical and interventional treatment planning of NET liver metastases.Key Points• Ga-68-DOTATOC PET–Gd-EOB-DTPA MRI fusion can improve imaging of liver metastases of neuroendocrine tumours.• This technique appears more sensitive than PET/CT for staging NET hepatic metastases. • Ga-68-DOTATOC PET–Gd-EOB-DTPA MRI fusion is more specific than MRI alone.

Outcome of uterine artery embolization versus MR-guided high-intensity focused ultrasound treatment for uterine fibroids: Long-term results

OBJECTIVES To compare the long-term outcome after uterine artery embolization (UAE) versus magnetic resonance-guided high-intensity focused ultrasound (MR-g HIFU) for symptomatic uterine fibroids. METHODS Seventy-seven women (median age, 39.3 years; range, 29.2-52.2 years) with symptomatic uterine fibroids, equally eligible for UAE and MR-g HIFU based on our exclusion criteria underwent treatment (UAE, N = 41; MR-g HIFU, N = 36) from 2002 to 2009 at our institution. Symptom severity (SS) and total health-related quality of life (Total HRQoL) scores were assessed by the uterine fibroid symptom and quality of life (UFS-QoL) questionnaire before treatment and at long-term follow-up after UAE (median 61.9 months) and after MR-g HIFU (median: 60.7 months). Re-intervention rates were assessed for each therapy and compared. RESULTS Re-intervention was significantly lower after UAE (12.2%) than after MR-g HIFU (66.7%) at long-term follow-up (p<0.001). After UAE changes in SS (50 pre-treatment vs. 6.3 post-treatment) and Total HRQoL (57.8 pre-treatment vs. 100 post-treatment) were significantly better than changes in SS (42.2 pre-treatment vs. 26.6 post-treatment) and Total HRQoL score (66.4 pre-treatment vs. 87.9 post-treatment) after MR-g HIFU (p = 0.019 and 0.049 respectively). CONCLUSIONS Improvement of SS and Total HRQoL scores was significantly better after UAE resulting in a significant lower re-intervention rate compared to MR-g HIFU.

Searching for primaries in patients with neuroendocrine tumors (NET) of unknown primary and clinically suspected NET: Evaluation of Ga-68 DOTATOC PET/CT and In-111 DTPA octreotide SPECT/CT

Abstract Background. To evaluate the clinical efficacy of In-111 DTPA octreotide SPECT/CT and Ga-68 DOTATOC PET/CT for detection of primary tumors in patients with either neuroendocrine tumor of unknown primary (NETUP) or clinically suspected primary NET (SNET). Patients and methods. A total of 123 patients were included from 2006 to 2009, 52 received Ga-68 DOTATOC PET/CT (NETUP, 33; SNET, 19) and 71 underwent In-111 DTPA octreotide SPECT/CT (50; 21). The standard of reference included histopathology or clinical verification based on follow-up examinations. Results. In the NETUP group Ga-68 DOTATOC detected primaries in 15 patients (45.5%) and In-111 DTPA octreotide in 4 patients (8%) (p < 0.001); in the SNET group, only 2 primaries could be detected, all by Ga-68 DOTATOC. In patients with NETUP, primary tumors could be found significantly more often than in patients with SNET (p = 0.01). Out of these 21 patients 14 patients were operated. Conclusion. Ga-68 DOTATOC PET/CT is preferable to In-111 DTPA octreotide SPECT/CT when searching for primary NETs in patients with NETUP but should be used with caution in patients with SNET.

Pulmonary FDG uptake without a CT counterpart – a pitfall in interpreting PET/CT images:

Abnormal pulmonary 18F-FDG foci may occur with benign lesions like pneumonia but seldomly without any pathological CT findings. We report the case of a focal pulmonary 18F-FDG uptake without CT correlate in an initial staging examination of a patient with squamous cell carcinoma of the base of the tongue. A follow-up study did not show any suspicious lesion in this area, but pneumonia with 18F-FDG uptake in another region of the lung. 18F-FDG foci without pathological CT are a rare finding and have been associated with emboli. In the literature two main mechanisms underlying focal 18F-FDG uptake in pulmonary embolism are mentioned: an inflammatory reaction of a pre-existing vascular thrombus and an iatrogenic microembolism caused during injection. In our case the 18F-FDG accumulation was assessed as an iatrogenic pulmonary microembolism.

Outcomes of Endobronchial Valve Treatment Based on the Precise Criteria of an Endobronchial Catheter for Detection of Collateral Ventilation under Spontaneous Breathing.

Background: Endoscopic lung volume reduction with valves is a valid therapeutic option for COPD patients with severe emphysema. The exclusion of interlobar collateral ventilation (CV) is an important predictor of clinical success. Objectives: Recently, a catheter-based endobronchial in vivo measurement system (Chartis, Pulmonx, USA) has become routine in the clinical evaluation of CV status in target lobes, but the criteria for phenotyping CV by Chartis evaluation have not yet been defined. We asked the questions, how many phenotypes can be identified using Chartis, what are the exact criteria to distinguish them, and how do the Chartis phenotypes respond to valve insertionκ Methods: In a retrospective study, 406 Chartis assessments of 166 patients with severe COPD were analyzed. Four Chartis phenotypes, CV positive (CV+), CV negative (CV-), low flow (LF) and low plateau were identified. Fifty-two patients without CV were treated with valves and followed for 3 months. Results: The Chartis phenotypes were discriminated with respect to decline in expiratory peak flow, increase in resistance index and change in total exhaled volume after 1, 2, 3, 4 and 5 min of measurement time (p < 0.0001, ANOVA), and the cutoff criteria were defined accordingly. To examine the application of these phenotyping criteria, students applied them to 100 Chartis assessments, and they demonstrated almost perfect inter- and intraobserver agreements (κ > 0.9). Compared to baseline, CV- and LF patients with ipsilateral CV- lobe showed an improvement in FEV1 (p < 0.05), vital capacity (p < 0.05) and target lobe volume reduction (p < 0.005) after valve insertion. Conclusion: This study describes the most prevalent Chartis phenotypes.

Modifying Post-Operative Medical Care after EBV Implant May Reduce Pneumothorax Incidence.

Objective Endoscopic lung volume reduction (ELVR) with valves has been shown to improve COPD patients with severe emphysema. However, a major complication is pneumothoraces, occurring typically soon after valve implantation, with severe consequences if not managed promptly. Based on the knowledge that strain activity is related to a higher risk of pneumothoraces, we asked whether modifying post-operative medical care with the inclusion of strict short-term limitation of strain activity is associated with a lower incidence of pneumothorax. Methods Seventy-two (72) emphysematous patients without collateral ventilation were treated with bronchial valves and included in the study. Thirty-two (32) patients received standard post-implantation medical management (Standard Medical Care (SMC)), and 40 patients received a modified medical care that included an additional bed rest for 48 hours and cough suppression, as needed (Modified Medical Care (MMC)). Results The baseline characteristics were similar for the two groups, except there were more males in the SMC cohort. Overall, ten pneumothoraces occurred up to four days after ELVR, eight pneumothoraces in the SMC, and only two in the MMC cohorts (p=0.02). Complicated pneumothoraces and pneumothoraces after upper lobe treatment were significantly lower in MMC (p=0.02). Major clinical outcomes showed no significant differences between the two cohorts. Conclusions In conclusion, modifying post-operative medical care to include bed rest for 48 hours after ELVR and cough suppression, if needed, might reduce the incidence of pneumothoraces. Prospective randomized studies with larger numbers of well-matched patients are needed to confirm the data.

Comparison of 68Ga-OPS202 (68Ga-NODAGA-JR11) and 68Ga-DOTATOC (68Ga-Edotreotide) PET/CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Evaluation of Sensitivity in a Prospective Phase II Imaging Study

Radiolabeled somatostatin (sst) receptor agonists are integral to the diagnosis of gastroenteropancreatic neuroendocrine tumors (NETs), but detection rates, especially of liver metastases, remain limited even with PET/CT. 68Ga-OPS202 (68Ga-NODAGA-JR11; NODAGA = 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid and JR11 = Cpa-c(dCys-Aph(Hor)-dAph(Cbm)-Lys-Thr-Cys)-dTyr-NH2)), a novel radiolabeled sst receptor antagonist with a high affinity for the sst2 receptor, has the potential to perform better than sst receptor agonists. Here, we present the results of the phase II component of a phase I/II study that evaluated the sensitivity of 68Ga-OPS202, compared with the reference compound, 68Ga-DOTATOC (an sst receptor agonist), in PET imaging. Methods: Patients received a single 150-MBq intravenous injection of 68Ga-DOTATOC (15 μg of peptide) and 2 single 150-MBq intravenous injections of 68Ga-OPS202 (15 μg of peptide at visit 1 and 50 μg at visit 2). Whole-body PET/CT acquisitions were performed 1 h after injection on the same calibrated PET/CT scanner. Diagnostic efficacy measures were compared against contrast medium–enhanced CT or MRI as the gold standard. Two independent masked experts read the scans, and both outcomes were combined for analysis. Results: Twelve consecutive patients with low- or intermediate-grade gastroenteropancreatic NETs took part in this prospective study. Image contrast for matched malignant liver lesions was significantly higher for the 68Ga-OPS202 scans than for the 68Ga-DOTATOC scan: the median of the mean tumor-to-background SUVmax ratios were significantly higher for 15 and 50 μg of 68Ga-OPS202 (5.3 and 4.3, with interquartile ranges of 2.9–5.7 and 3.4–6.3 and P values of 0.004 and 0.008) than for 68Ga-DOTATOC (1.9, with an interquartile range of 1.4–2.9). The higher tumor-to-background ratio of 68Ga-OPS202 resulted not only in a higher detection rate of liver metastases but also in a significantly higher lesion-based overall sensitivity with the antagonist than with 68Ga-DOTATOC: 94% and 88% for 50 and 15 μg of 68Ga-OPS202, respectively, and 59% for 15 μg of 68Ga-DOTATOC (P < 0.001). Positive predictive values for 68Ga-OPS202 PET/CT and 68Ga-DOTATOC PET/CT were similar (∼98%). There were no significant differences in image contrast, sensitivity, or positive predictive values between the 2 68Ga-OPS202 peptide doses, indicating a high reproducibility. Conclusion: Preliminary diagnostic efficacy data from this phase II study indicate that 68Ga-OPS202 has high sensitivity for the detection of gastroenteropancreatic NETs. Further studies in larger patient populations are warranted.

Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy.

The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR). However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT), St George’s Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI). These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001). TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012). Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001). This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR. Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1.

Detection of neuroendocrine tumours in the small intestines using contrast-enhanced multiphase Ga-68 DOTATOC PET/CT: the potential role of arterial hyperperfusion

Abstract Background. Interpretation of small intestinal neuroendocrine tumours (NETs) by Ga-68 DOTATOC PET/CT can be difficult. The potential benefit of arterial hyperperfusion for the detection of NETs was evaluated. Methods. Between 2006 and 2009, 320 consecutive Ga-68 DOTATOC PET/CT examinations, performed for NETs, revealed 40 lesions suggesting intestinal NETs in 25 patients. Two groups of lesions were distinguished: epigastric lesions evaluable in the arterial and venous CT scan (Group 1) and hypogastrial lesions evaluable in the venous CT scan only (Group 2). Lesions were jointly rated by two radiologists and a nuclear medicine physician. Maximum standard uptake values (SUVmax) of lesions and background were assessed. The reference standard was histology (available for 28 lesions) or follow-up (for a mean of 22.9 months). Results. PET detected all suspicious lesions but was false positive in 3 lesions. In Group 1 the arterial scan performed significantly better than the venous scan (p = 0.008). Diagnostic performance was better in Group 1 than in Group 2 (p < 0.001). SUVmax of true positive lesions were significantly higher than background SUVmax (p < 0.001) and SUVmax of false positive lesions (p = 0.005). Conclusions. The arterial phase of multiphase Ga-68 DOTATOC PET/CT might improve the localization of intestinal NETs and, thereby, improve the overall diagnostic accuracy of this modality in the assessment of intestinal NETs by adding information about lesion perfusion not available when only venous CT is performed

Optical imaging of breast cancer using hemodynamic changes induced by valsalva maneuver.

PURPOSE To investigate whether changes in hemodynamics induced by Valsalva maneuver can be exploited for detecting and characterizing breast lesions by optical mammography. MATERIALS AND METHODS 30 women underwent optical imaging of the breast using a DYNOT 232 system and performing Valsalva maneuvers prior to biopsy. Changes in light absorption due to changes in oxyhemoglobin and deoxyhemoglobin concentrations were recorded volumetrically and in a time-resolved manner. The parameters full width at half maximum (FWHM), time to ten (TTT), and peak amplitude (PA) of the reconstructed concentration time curves yielded color-coded maps of the breast which were separately evaluated by two experienced readers for detection rate, degree of visibility, and detection of additional lesions. ROC analysis was performed with the evaluation results. RESULTS 10 patients were excluded from analysis due to artifacts or inadequately performed Valsalva maneuver. The resulting 20 patients showed a clear increase in oxygenated and deoxygenated hemoglobin concentration after the onset of the Valsalva maneuver. ROC analysis yielded AUC values (0.393 - 0.779) that did not differ from random probabilities. The highest AUC values were obtained for FWHM (AUC: 0.779, detection rates [60 - 70 %], identification of additional lesions [55 - 70 %]). PA analysis had the highest detection rate (70 - 90 %) but also the highest identification of false-positive additional lesions (80 - 90 %). The concordance rates of the two readers for malignant lesions were satisfactory (0.524 - 1.0). CONCLUSION Our study revealed susceptibility to artifacts and a large number of false-positive additional lesions, suggesting that the evaluation of hemodynamic changes after Valsalva maneuver by optical imaging is not a promising method.