Transverse vs. median laparotomy in peritonitis and staged lavage: a single center case series.

Background: Staged lavage was first introduced in the 1970s and now serves as a therapeutic option for septic patients with peritonitis. A central aspect of this treatment concept is leaving the abdomen open after a wide incision. To evaluate the influence of transverse vs. median access to the abdomen in staged lavage, data from the authors' patients were analyzed. Methods: To evaluate patients with peritonitis, prospective intensive care data were examined together with data on the surgical details. The main aspects covered here were the surgical details of the lavage (namely, transverse vs. median laparotomy), number of lavages, fascia closure, wound-healing disorders, and observed lethality, in combination with the preoperatively evaluated SAPS-II score, expected hospital lethality, patient age, and the Mannheim Peritonitis Index. Results: Between January 2008 and December 2018, 522 patients were treated with open abdomen and staged lavage. The mean age of the patients was 66.0 years (standard deviation (SD) 15.9 years). A median incision was used in 140 cases, and transverse laparotomy was performed in 382. The mean SAPS-II score was 46.5 (SD 15.7), expected lethality was 39.6% (SD 26.3%), and observed lethality was 19.9%. On average, two lavages were performed after the index operation. Transverse incision was significantly less likely to cause wound-healing disorder (p=0.03), and fascial dehiscence was observed less frequently in the transverse laparotomies group than in median incisions in the statistical trend (p=0.06). Conclusion: In summary, staged lavage reduced expected lethality in patients with peritonitis. Transverse incision caused wound-healing disorders and fascial dehiscence less often. Therefore, the indication for transverse laparotomy should be generous, as this form of treatment is advantageous in case of peritonitis.

PET imaging of cardiac wound healing using a novel [68Ga]-labeled NGR probe in rat myocardial infarction.

PURPOSE: Peptides containing the asparagine-glycine-arginine (NGR) motif bind to aminopeptidase N (CD13), which is expressed on inflammatory cells, endothelial cells, and fibroblasts. It is unclear whether radiolabeled NGR-containing tracers could be used for in vivo imaging of the early wound-healing phase after myocardial infarction (MI) using positron emission tomography (PET). PROCEDURES: Uptake of novel tracer [(68)Ga]NGR was assessed together with [(68)Ga]arginine-glycine-aspartic acid ([(68)Ga]RGD) and 2-deoxy-2-[(18) F]fluoro-D-glucose after myocardial ischemia/reperfusion (MI/R) injury using µ-PET and autoradiography, and relative expressions of CD13 and integrin ß3 were assessed in fibroblasts, inflammatory cells, and endothelial cells by immunohistochemistry. RESULTS: In the infarcted myocardium, uptake of [(68)Ga]NGR was maximal from days 3 to 7 after MI/R, and correlated with fibroblast and inflammatory cell infiltration as well as [(68)Ga]RGD uptake. CONCLUSIONS: [(68)Ga]NGR allows noninvasive and sequential determination of CD13 expression in fibroblasts and inflammatory cells by PET. This will facilitate monitoring of CD13 in the individual wound healing processes, allowing patient-specific therapies to improve outcome after MI.

Targeting P-selectin by gallium-68-labeled fucoidan positron emission tomography for noninvasive characterization of vulnerable plaques: correlation with in vivo 17.6T MRI.

OBJECTIVE: Nuclear imaging of active plaques still remains challenging. Advanced atherosclerotic plaques have a strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques, but not on the endothelium overlying inactive fibrous plaques. We proposed a new approach for noninvasive in vivo characterization of P-selectin on active plaques based on (68)Ga-Fucoidan, which is a polysaccharidic ligand of P-selectin with a nanomolar affinity. APPROACH AND RESULTS: (68)Ga-Fucoidan was tested for its potential to discriminate vulnerable plaques on apolipoprotein E-deficient mice receiving a high cholesterol diet by positron emission tomography and in correlation with 17.6T MRI. Furthermore, (68)Ga-Fucoidan was evaluated on endothelial cells in vitro and ex vivo on active plaques using autoradiography. The cellular uptake rate was increased ≈2-fold by lipopolysaccharide induction. Interestingly, on autoradiography, more intensive tracer accumulation at active plaques with thin fibrous caps and high-density foam cells were observed in comparison with a weaker focal uptake in inactive fibrous plaque segments (R=1.7±0.3; P<0.05) and fatty streaks (R=2.4±0.4; P<0.01). Strong uptake of radiotracer colocalized with increased P-selectin expression and high-density macrophage. Focal vascular uptake (mean of target to background ratio=5.1±0.8) of (68)Ga-Fucoidan was detected in all apolipoprotein E-deficient mice. Anatomic structures of plaque were confirmed by 17.6T MRI. The autoradiography showed a good agreement of (68)Ga-Fucoidan uptake with positron emission tomography. CONCLUSIONS: Our data suggest that (68)Ga-Fucoidan represents a versatile imaging biomarker for P-selectin with the potential to specifically detect P-selectin expression using positron emission tomography and to discriminate vulnerable plaques in vivo.

PET imaging with [68Ga]NOTA-RGD for prostate cancer: a comparative study with [¹8F]fluorodeoxyglucose and [¹8F]fluoroethylcholine.

The α(v)ß3 integrin is highly expressed in prostate cancer (PCa), in which it is a key player in tumour invasion, angiogenesis and metastasis formation. Therefore, α(v)ß3 integrin is considered a very promising target for molecular imaging of PCa. This study tested the potential of the novel α(v)ß3 integrin affine agent [68Ga]NOTA-RGD in comparison with the established [¹8F]fluoroethylcholine (FEC) and [¹8F]fluorodeoxyglucose (FDG) for assessing PCa using positron emission tomography (PET). [68Ga]NOTA-RGD showed a lower uptake in PC-3 and DU-145 cells compared with FEC and FDG. µPET imaging studies showed a good delineation of the PCa xenografts in mice. The means tumor-to-muscle and tumor-to-bone-ratio amounted 5.1 ± 1.4 and 5.2 ± 1.2 for [68Ga]NOTA-RGD compared with 2.6 ± 0.9 and 2.9 ± 1.6 for FDG, and 2.4 ± 0.7 and 0.8 ± 0.2 for FEC, respectively. The uptake of [68Ga]NOTA-RGD into tumor was fully inhibited by c(RGDfV), known to bind specifically to α(v)ß3 integrin, confirming the specificity of the tumor uptake in vivo. These results suggest that [68Ga]NOTA-RGD is a promising candidate for PET imaging of α(v)ß3 integrin expression in PCa and warrant further in vivo validations to ascertain its potential as an imaging agent for clinical use. The simple and fast preparation of [68Ga]NOTA-RGD may greatly facilitate its translation to a clinical setting.

Small-animal PET imaging of isolated perfused rat heart.

UNLABELLED: The assessment of myocardial radiotracer kinetics, including cardiac extraction fraction and washout, requires the study of isolated perfused hearts to avoid analytic error due to tracer recirculation and systemic metabolites. Analysis of the isolated perfused rat heart by a high-resolution small-animal PET system may offer both reliable evaluation of cardiac tracer kinetics and tomographic images. METHODS: An isolated perfused heart system was modified to accommodate the small PET gantry bore size. Isolated rat hearts were perfused via the Langendorff method under a constant flow of Krebs-Henseleit buffer containing (18)F-FDG with a rate of 5 mL/min and placed in the field of view of the commercially available small-animal PET system. Dynamic PET imaging was then performed, with (18)F-FDG uptake in the isolated perfused heart verified by γ counter measurements. Additionally, a rat heart of myocardial infarction was also studied in this system with static PET imaging. RESULTS: Dynamic PET acquisition of the isolated heart under constant (18)F-FDG infusion demonstrated continuous increase of activity in the heart. Correlation between cardiac activity (MBq) measured with the PET system and measurements made with the γ counter were excellent (R(2) = 0.98, P < 0.001, n = 10). Tracer input rate (MBq/min) was also well correlated with cardiac tracer uptake rate (MBq/min) (R(2) = 0.87, P < 0.001, n = 12). PET imaging of the heart with myocardial infarction showed a clear tracer uptake defect corresponding to the location of scar tissue identified by autoradiography and histology. CONCLUSION: Combining the Langendorff method of isolated rat heart perfusion with high-resolution small-animal PET allows for the reliable quantification of myocardial tracer kinetics. This novel assay is readily adapted to available small-animal PET systems and may be useful for understanding myocardial PET tracer kinetics.

Compressed sensing for reduction of noise and artefacts in direct PET image reconstruction.

AIM: Image reconstruction in positron emission tomography (PET) can be performed using either direct or iterative methods. Direct reconstruction methods need a short reconstruction time. However, for data containing few counts, they often result in poor visual images with high noise and reconstruction artefacts. Iterative reconstruction methods such as ordered subset expectation maximization (OSEM) can lead to overestimation of activity in cold regions distorting quantitative analysis. The present work investigates the possibilities to reduce noise and reconstruction artefacts of direct reconstruction methods using compressed sensing (CS). MATERIALS AND METHODS: Raw data are generated either using Monte Carlo simulations using GATE or are taken from PET measurements with a Siemens Inveon small-animal PET scanner. The fully sampled dataset was reconstructed using filtered backprojection (FBP) and reduced in Fourier space by multiplication with an incoherently undersampled sampling pattern, followed by an additional reconstruction with CS. Different sampling patterns are used and an average of the reconstructions is taken. The images are compared to the results of an OSEM reconstruction and quantified using signal-to-noise ratio (SNR). RESULTS: The application of the proposed CS post-processing technique clearly improves the image contrast. Dependent on the undersampling factor, noise and artefacts are reduced resulting in an SNR that is increased up to 3.4-fold. For short acquisition times with low count statistics the SNR of the CS reconstructed image exceeds the SNR of the OSEM reconstruction. CONCLUSION: Especially for low count data, the proposed CS-based post-processing method applied to FBP reconstructed PET images enhances the image quality significantly.

Specific somatostatin receptor II expression in arterial plaque: (68)Ga-DOTATATE autoradiographic, immunohistochemical and flow cytometric studies in apoE-deficient mice.

BACKGROUND: The rupture of atherosclerotic plaques is triggered by inflammation. Specific detection of inflammation is therefore the focus of many investigations. Noninvasive imaging methods, such as positron emission tomography (PET), also are suited for this purpose. (68)Ga-DOTATATE is a (68)Ga-labeled radiotracer with specific affinity to somatostatin receptor subtype-2 (SSTR-2). SSTR-2 was found specifically expressed on human macrophages/monocytes. OBJECTIVE: We aimed to confirm the distribution of SSTR-2 in inflammatory plaques, and to assess its co-localization with macrophages within the plaques. We also assessed (68)Ga-DOTATATE uptakes in plaques by autoradiography. METHOD: Apolipoprotein E (ApoE)-/- mice on a high-cholesterol diet were injected with (68)Ga-DOTATATE. The animals were sacrificed and aorta sections were examined using autoradiography and immunohistochemistry. Furthermore, expression of SSTR-2 was analyzed by flow cytometry. Western blot was conducted to assess SSTR-2 regulation in basal and lipopolysaccharide (LPS)-activated state. To evaluate the specificity of the (68)Ga-DOTATATE, the sections were pre-incubated with monoclonal SSTR-2 antibody before autoradiography. RESULT: Autoradiographic imaging showed uptake of (68)Ga-DOTATATE co-localized with the macrophage-rich plaques by immunohistochemical examination. A high expression of SSTR-2 on macrophages was found by flow cytometry and western blot. Stimulation with lipopolysaccharide did not alter expression of SSTR-2 in macrophages. CONCLUSION: Due to its specific binding to macrophages, (68)Ga-DOTATATE might be a suitable radiotracer for the evaluation of inflammatory activity in unstable plaques.