PSMA PET/CT vs. CT alone in newly diagnosed biochemical recurrence of prostate cancer after radical prostatectomy: Comparison of detection rates and therapeutic implications.

OBJECTIVES: To compare prostate specific membrane antigen (PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) and computed tomography (CT) alone for the detection of biochemical recurrence of prostate cancer (PCa) and effect on treatment. METHODS: This retrospective study included 59 patients with recently recorded biochemical recurrence of PCa (mean PSA 1.96 ± 1.64 ng/mL) after radical prostatectomy. Patients received PET/CT with either 68Ga-PSMA-11 (n = 36) or 18F-PSMA-1007 (n = 23). PET/CT and CT images were evaluated separately in regard to PCa lesion count, type, and localisation by two physicians. Histopathology, follow-up imaging and PSA levels after salvage irradiation served as reference standard. A McNemar test was used to compare detection rates. Changes in therapeutic approaches based on staging differences between CT alone and PET/CT were assessed in a virtual multidisciplinary tumour board. RESULTS: There were 142 lesions in 50 of 59 patients. PSMA PET/CT detected 141 lesions (99.3 %) in 50 patients (84.7 %), while CT detected 72 lesions (50.7 %) in 29 patients (49.2 %). A significantly higher detection rate of PSMA PET/CT was observed on a lesion-based analysis (p < 0.0001) and on a patient based analysis (p < 0.0001). Herein, both 68Ga- and 18F-PSMA PET/CT performed significantly better than CT alone (p < 0.0001, respectively). In 9 patients (15.3 %) no relapse was detectable by either modality. All lesions detected by CT were also detected by PSMA PET/CT. In 38 patients PSMA PET/CT detected more lesions than CT alone, altering the treatment approach in 22 of these patients. CONCLUSION: PSMA PET/CT is superior to CT alone in detecting biochemical recurrence in PCa patients after radical prostatectomy and offered additional therapeutic options in a substantial number of patients.

Advanced diffusion weighted imaging of the prostate: Comparison of readout-segmented multi-shot, parallel-transmit and single-shot echo-planar imaging.

PURPOSE: This study evaluates objective and subjective image quality (IQ) of three different diffusion weighted imaging (DWI) sequences in prostate MRI at 3.0 Tesla within the same patients. METHOD: Thirty-six consecutive patients (70 ± 8 years) with multi-parametric prostate MRI (mp-MRI; 3 T) and subsequently verified prostate cancer (PCa) by targeted plus systematic MR/US-fusion biopsy from 03/2016 to 12/2017 were included. Readout-segmented (rs) multi shot echo-planar imaging (EPI), parallel transmit (ptx) EPI, and single-shot (ss) EPI with b-values of 0, (500,) 1,000 s/mm² and calculated b1,500 were prospectively acquired of every patient. Signal intensities (SI) of PCa and benign tissue (peripheral and transition zone; PZ and TZ) in ADC, b1,000, and calculated b1,500 images were analyzed. Endpoints were signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and subjective IQ on a 5-point scale by two blinded readers. RESULTS: For ss-EPI ADC, b-values of 1,000, and calculated 1,500 s/mm² images showed a higher SNR compared to rs-EPI and ptx-EPI (p < 0.01). CNR of PCa and benign tissue was significantly higher for rs-EPI in high b value images compared to ptx-EPI and ss-EPI (p < 0.01). Subjective IQ was significantly higher for rs-EPI (p < 0.01). Significantly higher ADC reduction combined with signal increase on high b value images for PCa compared to the surrounding healthy tissue in PZ and TZ (PCa contrast intensity) was detected for rs-EPI (p < 0.01). Single PCa lesions could only be recognized and correlated on rs-EPI. CONCLUSIONS: Rs-EPI and ptx-EPI were superior to ss-EPI regarding contrast intensity of PCA, but inferior regarding SNR. Subjective imaging parameters were superior for rs-EPI. Especially rs-EPI, but also ptx-EPI might improve and faciliate prostate cancer detection, rs-EPI at the expense of a longer acquisition time.

Quality assurance in CT: implementation of the updated national diagnostic reference levels using an automated CT dose monitoring system.

AIM: To evaluate the implementation of the updated computed tomography (CT) diagnostic reference levels (DRLs) from the German Federal Office for Radiation Protection into clinical routine using an automatic CT dose monitoring system. METHODS AND MATERIALS: CT radiation exposure was analysed before and after implementing the updated national DRLs into routine clinical work in 2016. After the implementation process, institutional CT protocols were mapped to the anatomical regions for which DRLs were provided. Systematically, protocols that exceeded the thresholds were optimised and analysed in detail. The CT radiation output parameters analysed were volumetric CT dose index (CTDIvol) and dose-length product (DLP). Three radiologists evaluated subjective image quality using a three-point Likert scale. RESULTS: The study included 94,258 CT series (from 27,103 CT examinations) in adult patients performed in 2016. When averaged over all body regions with available DRL, institutional CTDIvol/DLP values were always below the DRLs (65.2±32.9%/67.3±41.5% initially; 59.4±32%/60.5±39.9% after optimisation). Values exceeding the national DRLs were found for pelvis (n=268; CTDIvol 107.7±65.7%/DLP 106.3±79.3%), lumbar spine (n=91; 160.8±74.7%/175.2±104.1%), and facial bones (n=527; 108±39%/152.7±75.7%). After optimisation, CTDIvol and DLP were 87.9±73%/87.8±80.8% for the pelvis, 67.8±33.2%/74.5±50.6% for the lumbar spine and 95.1±45.8%/133.3±74.6% for the viscerocranium. CONCLUSION: An automatic CT dose monitoring system enabled not only comprehensive monitoring of a DRL implementation process but can also help to optimise radiation exposure.

Iterative metal artefact reduction in CT: can dedicated algorithms improve image quality after spinal instrumentation?

AIM: To investigate the value of dedicated computed tomography (CT) iterative metal artefact reduction (iMAR) algorithms in patients after spinal instrumentation. MATERIALS AND METHODS: Post-surgical spinal CT images of 24 patients performed between March 2015 and July 2016 were retrospectively included. Images were reconstructed with standard weighted filtered back projection (WFBP) and with two dedicated iMAR algorithms (iMAR-Algo1, adjusted to spinal instrumentations and iMAR-Algo2, adjusted to large metallic hip implants) using a medium smooth kernel (B30f) and a sharp kernel (B70f). Frequencies of density changes were quantified to assess objective image quality. Image quality was rated subjectively by evaluating the visibility of critical anatomical structures including the central canal, the spinal cord, neural foramina, and vertebral bone. RESULTS: Both iMAR algorithms significantly reduced artefacts from metal compared with WFBP (p<0.0001). Results of subjective image analysis showed that both iMAR algorithms led to an improvement in visualisation of soft-tissue structures (median iMAR-Algo1=3; interquartile range [IQR]:1.5-3; iMAR-Algo2=4; IQR: 3.5-4) and bone structures (iMAR-Algo1=3; IQR:3-4; iMAR-Algo2=4; IQR:4-5) compared to WFBP (soft tissue: median 2; IQR: 0.5-2 and bone structures: median 2; IQR: 1-3; p<0.0001). Compared with iMAR-Algo1, objective artefact reduction and subjective visualisation of soft-tissue and bone structures were improved with iMAR-Algo2 (p<0.0001). CONCLUSION: Both iMAR algorithms reduced artefacts compared with WFBP, however, the iMAR algorithm with dedicated settings for large metallic implants was superior to the algorithm specifically adjusted to spinal implants.

Timing of Mean Transit Time Maximization is Associated with Neurological Outcome After Subarachnoid Hemorrhage.

PURPOSE: Computed tomography perfusion (CTP) has gained significant relevance for the radiological screening of patients at risk of developing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Particularly, the impact of MTTPEAK, i.e., the maximal mean transit time value in a series of CTP measurements, for the prediction of long-term outcome has recently been demonstrated by our group. Complementing this recent work, the present study investigated how the timing of MTTPEAK affected the long-term outcome after aneurysmal subarachnoid hemorrhage. METHODS: CTP examinations from 103 patients with clinical deterioration attributed to DCI after aSAH were retrospectively analyzed for time interval between SAH ictus and onset of MTTPEAK in association with modified Rankin Scale (mRS) 23.1 months after SAH. RESULTS: Patients with unfavorable outcome (mRS > = 2) suffered significant earlier MTTPEAK onsets than patients with favorable outcome (mRS = 0 and 1). MTTPEAK within the first week was associated with significantly higher mRS scores compared to later MTTPEAK. Timing of MTTPEAK together with the value of MTTPEAK and initial World Federation of Neurosurgical Societies (WFNS) grade was a significant predictor for an unfavorable outcome (mRS > = 2). CONCLUSIONS: The current findings suggest a presumably higher vulnerability of the brain to early microcirculatory impairments after aSAH and highlight that timing of MTT elevations could be considered for the identification of patients at increased risk for poor neurological outcome due to DCI.

Cloud-Based CT Dose Monitoring using the DICOM-Structured Report: Fully Automated Analysis in Regard to National Diagnostic Reference Levels.

PURPOSE: To implement automated CT dose data monitoring using the DICOM-Structured Report (DICOM-SR) in order to monitor dose-related CT data in regard to national diagnostic reference levels (DRLs). MATERIALS AND METHODS: We used a novel in-house co-developed software tool based on the DICOM-SR to automatically monitor dose-related data from CT examinations. The DICOM-SR for each CT examination performed between 09/2011 and 03/2015 was automatically anonymized and sent from the CT scanners to a cloud server. Data was automatically analyzed in accordance with body region, patient age and corresponding DRL for volumetric computed tomography dose index (CTDIvol) and dose length product (DLP). RESULTS: Data of 36,523 examinations (131,527 scan series) performed on three different CT scanners and one PET/CT were analyzed. The overall mean CTDIvol and DLP were 51.3% and 52.8% of the national DRLs, respectively. CTDIvol and DLP reached 43.8% and 43.1% for abdominal CT (n=10,590), 66.6% and 69.6% for cranial CT (n=16,098) and 37.8% and 44.0% for chest CT (n=10,387) of the compared national DRLs, respectively. Overall, the CTDIvol exceeded national DRLs in 1.9% of the examinations, while the DLP exceeded national DRLs in 2.9% of the examinations. Between different CT protocols of the same body region, radiation exposure varied up to 50% of the DRLs. CONCLUSION: The implemented cloud-based CT dose monitoring based on the DICOM-SR enables automated benchmarking in regard to national DRLs. Overall the local dose exposure from CT reached approximately 50% of these DRLs indicating that DRL actualization as well as protocol-specific DRLs are desirable. The cloud-based approach enables multi-center dose monitoring and offers great potential to further optimize radiation exposure in radiological departments. KEY POINTS: • The newly developed software based on the DICOM-Structured Report enables large-scale cloud-based CT dose monitoring • The implemented software solution enables automated benchmarking in regard to national DRLs • The local radiation exposure from CT reached approximately 50 % of the national DRLs • The cloud-based approach offers great potential for multi-center dose analysis.

Impact of organ-specific dose reduction on the image quality of head and neck CT angiography.

OBJECTIVES: Organ-specific dose reduction (OSDR) algorithms can reduce radiation on radiosensitive organs up to 59 %. This study evaluates the influence of a new OSDR algorithm on image quality of head and neck computed tomographic angiography (CTA) in clinical routine. METHODS: Sixty-two consecutive patients (68 ± 13 years) were randomised into two groups and imaged using 128-row multidetector CT. Group A (n = 31) underwent conventional CTA and group B (n = 31) CTA with a novel OSDR algorithm. Subjective and objective image quality were statistically compared. Subjective image quality was rated on a five-point scale. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated with region-of-interest measurements. RESULTS: The SNR of the common carotid artery and middle cerebral artery was 53.6 ± 22.7 and 43.3 ± 15.3 (group A) versus 54.1 ± 20.5 and 46.2 ± 14.6 (group B). The CNR was 40.0 ± 19.3 and 29.7 ± 12.0 (group A) compared with 40.7 ± 16.8 and 32.9 ± 10.9 (group B), respectively. Subjective image quality was excellent in both groups (mean score 4.4 ± 0.7 versus 4.4 ± 0.6). Differences between the two groups were not significant. CONCLUSIONS: The novel OSDR algorithm does not compromise image quality of head and neck CTA. Its application can be recommended for CTA in clinical routine to protect the thyroid gland and ocular lenses from unnecessary high radiation. KEY POINTS: • Organ-specific dose reduction (OSDR) can significantly reduce radiation exposure during CT • OSDR does not compromise image quality of head and neck CTA • OSDR can significantly lower the risk of radiation damage to sensitive organs • OSDR can easily be applied in routine clinical practice.

Healing of laser-induced tympanic membrane perforations in rats: no contribution of granulocyte colony-stimulating factor or Gelfoam.

OBJECTIVES: To study whether granulocyte colony-stimulating factor together with Gelfoam (absorbable gelatin sponge, USP) could enhance the healing of freshly perforated tympanic membranes. The frequency and occurrence of different immunocompetent cells and collagen types was noted. METHODS: Laser perforations were made in the tympanic membrane of rats that were sacrificed at different time intervals post-myringotomy: Day 1, 3, 6, and 12. Tympanic membrane specimens were embedded and sections were stained with hematoxylin/eosin and an immunohistochemical technique was used, with antibodies against macrophages, B-cells, T-cells, and type I-IV collagens. Semi-quantification was performed after counting positive cells, mean values were calculated and analyzed statistically. RESULTS: All perforations, except one, had closed by Day 12 and no difference was observed between experimental and control ears at the other time points. Gelfoam was still present in a high amount at Day 12. The sections were initially stained positive for type I and II collagen, but after Day 6, the regenerating tissue stained positive for mainly type III and IV collagens. Results showed that the recruitment of macrophages, B-cells, and T-cells could not be mapped with a statistical significance. CONCLUSIONS: This study showed that at 6-12 days post-laser myringotomy, type III and IV collagen has replaced the collagen type II that normally constitutes the healthy tympanic membrane. There is a concern for excessive scarring involving adjacent structures. It was also seen that the combination of Gelfoam and granulocyte colony-stimulating factor or saline did not affect the healing times in perforated tympanic membranes. No significant results regarding the inflammatory cell recruitment could be obtained on the studied time points or between experimental and control ears, except for in the Gelfoam matrix.

[Value of procalcitonin measurement in maternal fetal infection]. / Apport de la procalcitonine dans le diagnostic des infections materno foetales.

BACKGROUND: Materno foetal infection (MFI) remains one of the major causes of neonatal morbidity and mortality. Early detection of neonatal sepsis can be difficult, because the first signs of the disease may be unspecific and similar to symptoms of other non-infectious processes. AIM: We aimed to investigate the role of procalcitonin (PCT) in the diagnosis of fetal infection (MFI), and to compare it with those of the C-reactive protein (CRP). METHODS: We have conducted a prospective study during 20 months: which concerned 25 newborns suspected of MFI and admitted before 12 hours of life. All newborn had anamnestic and/or physical signs of possible infection. MFI was confirmed in newborns with positive bacterial analysis. CRP and PCT were determined in the sera at H12, H24, H36 and H48. Newborns were divided into: patients with recognized MFI (group 1), patients with possible MFI (group2) and non infected newborns (group 3): RESULTS: The specificity of PCT was 80% versus 27% for the CRP. Negative predictive value of PCT was 85% versus 66% for the CRP. The mean values, at H12, H24, H36 and H48, of PCT for newborn who had MFI were statistically grater than those for no infused group (p<0.05). No statistical difference was observed concerning CRP values. CONCLUSIONS: PCT may a useful tool in early diagnosing of MFI; it has better specificity and negative predictive value than CRP.

Tissue levels of histamine, PAF-acether and lysopaf-acether in carrageenan-induced granuloma in rats.

The tissue concentrations of several inflammatory mediators were determined from day 0 to day 60 in granuloma induced in rats (n = 105) by injection of carrageenan in the fascia of the latissimus dorsi muscle. Noncollagen proteins (NCP) and the number of polymorphonuclear leukocytes (PMN) and mast cells were also assessed. In comparison with the tissue at time 0, we noted in the inflamed tissue (at 4 h) an increase in total proteins (4.0 +/- 3.0 vs. 84 +/- 12.0%, mean +/- SEM) and PMN (0.0 +/- 0.0 vs. 43.3 +/- 13.4%), and a fall in histamine concentration (from 30.0 +/- 9.0 to 9.0 +/- 4.0 ng/ml). A partial disappearance of mast cells and an increase of PAF-acether (PAF) levels (1.0 +/- 1.0 vs. 30.0 +/- 22.0 ng/ml) was noted at 16 h, whereas lysopaf remained unchanged (3.7 +/- 4.0 vs. 3.5 +/- 1.0 ng/ml). During evolution towards chronic inflammation (day 10-60), NCP decreased, PMN disappeared and mast cells reappeared; the histamine level rose to 11.0 +/- 2.0 mg/ml, thus not reaching back baseline values. Lysopaf rose to 7.1 +/- 12.2 ng/ml and PAF levels increased further to reach 240.0 +/- 153.0 ng/ml at day 10. This study suggests that PAF may contribute to the acute phase of an inflammatory state such as the carrageenan-induced granuloma and that it is also present during the chronic process.

Biochemical and cellular effects of heparin-protamine injection in rabbits are partially inhibited by a PAF-acether receptor antagonist.

The origin of the thrombocytopenia and leucopenia induced by protamine-heparin complexes is unknown. We studied the biochemical and cellular effects of protamine (6 mg x kg-1, i.v.) injected after heparin (5 mg x kg-1, i.v.) in New Zealand rabbits. After protamine injection (0.5 min) increases in blood platelet-activating factor (PAF-acether, PAF) (27.6 +/- 27.6 to 148.2 +/- 48.9 pg x ml-1, P < 0.05), thrombocytopenia (403 +/- 64 to 166 +/- 13 cells x 10(-3) x mm-3, P < 0.05) and leucopenia (7650 +/- 930 to 4300 +/- 668 cells x mm-3, P < 0.05) were noted. Plasma thromboxane B2 increased at 1 min (125.6 +/- 24.4 to 879.7 +/- 141.0 pg x ml-1, P < 0.01). Protamine alone induced no change. Indomethacin (3 mg x kg-1, i.v.) did not counteract the effects of heparin-protamine. Pretreatment with the PAF receptor antagonist BN 52021 [9H1, 7a-(epoxymethano)-1 H,6aH-cyclopenta[c]furo[2,3-b]furo-[3',2',3,4]cyclopenta[1,2-d]fur an-5,9, 12(4H)trione,3-tert-butylhexahydro-4,7b,11 hydroxy-8 methyl] alone (3 mg x kg-1, i.v.) delayed thrombocytopenia and reduced plasma thromboxane B2 concentration but did not modify leucopenia. Thus thrombocytopenia and thromboxane B2 release triggered by heparin-protamine may be potentiated by the release of PAF.

Treatment of carrageenan induced arthritis by the platelet activating factor antagonist BN 50730.

OBJECTIVE: To evaluate the role of platelet activating factor (PAF) in the early stage of arthritis. METHODS: Arthritis was induced in rabbits by weekly intra-articular injections of carrageenan. A PAF receptor antagonist, BN 50730, was used as a preventive or curative agent. RESULTS: BN 50730 was able partially to prevent the development of arthritis, and was also active on established arthritis. The joint arthritis scores of BN treated animals were significantly lower than those of the non-treated animals. The blood concentrations of PAF, PAF bound to lipoproteins (lipo-PAF), and its precursor, lyso-PAF, were not correlated with clinical variations. CONCLUSIONS: The present data demonstrate a therapeutic action of a PAF antagonist in experimental arthritis and suggest a critical role for PAF during the early stage of arthritis.

Correlations between PAF-acether and tumor necrosis factor in rheumatoid arthritis. Influence of parenteral corticosteroids.

The aim of this study was to evaluate the presence of PAF-acether (PAF), its specific degrading enzyme acetylhydrolase, and tumor necrosis factor (TNF) concentrations in blood and synovial fluid (SF) from patients with active RA. The variations of the mediators were also evaluated after corticosteroid perfusions in 7 patients. Lipo-PAF (PAF complexed to lipoproteins) was the main form of PAF detected both in blood and in SF, whereas unbound PAF was uncommon. Acetylhydrolase activity was also present in SF, with a strong correlation between serum and SF levels. TNF was detected in most of the samples, and TNF and acetylhydrolase levels were strongly correlated both in blood and in SF. Despite dramatic clinical improvement, corticosteroid treatment was not accompanied by a significant reduction of the concentration of blood mediators, suggesting that these molecules should not be considered as markers of disease activity.

Role of paf-acether in protamine-induced thrombocytopenia in rabbits.

The effects of protamine (6 mg kg-1) injected after heparin (5 mg kg-1) have been studied in five groups of five New Zealand white rabbits. Group I was treated with the sequence heparin-protamine and group II with protamine alone. The animals of groups III and IV received respectively intravenous indomethacin (3 mg kg-1) and BN 52021 (3 mg kg-1), a paf receptor antagonist before the sequence heparin-protamine. Group V was pre-treated with indomethacin and BN 52021 before heparin reversal with protamine. In group I, immediate thrombocytopenia (44.1 +/- 4.6% of baseline level, P less than 0.05) and leucopenia (55.5 +/- 2.3% of baseline level, P less than 0.05) were observed 30 s after protamine reversal of heparin, paralleled with an increase in blood paf levels (27.6 +/- 27.6 vs. 148.2 +/- 48.9 pg ml-1, P less than 0.05). In group II, protamine alone induced no change in platelet count nor in blood paf levels (55 +/- 10 vs. 52.5 +/- 20 pg ml-1, P greater than 0.05). Pre-treatment with indomethacin alone (group III) did not protect the animals against the haematological changes induced by the heparin-protamine complexes. Pre-treatment with the paf receptor antagonist, alone or in association with indomethacin, delayed the occurrence of thrombocytopenia 3 min after protamine administration but the leucopenia was the same as in group I. This study demonstrated that paf is implicated in the immediate thrombocytopenia occurring after protamine reversal of heparin in rabbit.

Modulation of the contractile activity of the guinea-pig lung parenchymal strip by exogenous 5,8,11,14,17-eicosapentaenoic acid.

Exogenous eicosapentaenoic acid (EPA, 16.5 mumol/l or 33 mumol/l) inhibited dose-dependently the anaphylactic contractile response of guinea-pig lung parenchymal strips suspended in an organ bath. As determined by radioimmunoassay, EPA inhibited in a dose-dependent manner the anaphylactic release of the cyclooxygenase products thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1 alpha but simultaneously enhanced the release of sulfidopeptide (SP)-leukotrienes (LT). Indomethacin (2.8 mumol/l) abolished the release of cyclooxygenase products but potentiated the release of SP-LT. However, indomethacin treatment did not affect the inhibitory action of EPA on the contractile response of the anaphylactic lung strips. The lipoxygenase inhibitor, esculetin (50 mumol/l), inhibited the release of SP-LT and also that of cyclooxygenase products of polyunsaturated fatty acid metabolism. The combination of esculetin and EPA resulted in enhanced inhibition of the anaphylactic contractile response as compared to EPA alone. By reversed phase high pressure liquid chromatography (HPLC), SP-LT from anaphylactic lung parenchymal strips was shown to consist of LTD4 and LTE4. EPA-pretreated lung strips released upon immunologic challenge additional immunoreactivity comigrating with authentic LTC4, LTC5, LTD5 and LTE5. While anaphylactic control strips also released LTB4, in the bath fluid of EPA-treated strips, an additional immunoreactive compound migrating with the retention time of LTB5 was observed. In non-sensitized guinea-pig lung parenchymal strips EPA inhibited the myotropic activity of exogenous mediators such as histamine (9 mumol/l), LTC4 (16 nmol/l) and the TX mimetic U 46619 (28.4 nmol/l), an effect which was neither affected by indomethacin (2.8 mumol/l) nor by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)