Cardiac Computed Tomography Versus Transesophageal Echocardiography for the Detection of Left Atrial Appendage Thrombus: A Systemic Review and Meta‐Analysis

Background Transesophageal echocardiography (TEE) has been considered the gold standard for left atrial appendage (LAA) thrombus detection. Nevertheless, TEE may sometimes induce discomfort and cause complications. Cardiac computed tomography has been studied extensively for LAA thrombus detection. We performed this systemic review and meta‐analysis to assess the diagnostic accuracy of cardiac computed tomography for LAA thrombus detection compared with TEE. Methods and Results A systemic search was conducted in the PubMed, Embase, and Cochrane Library databases from January 1977 to February 2021. Studies performed for assessment diagnostic accuracy of cardiac computed tomography on LAA thrombus compared with TEE were included. Summary sensitivity, specificity, and posterior probability of LAA thrombus was calculated by using bivariate random‐effects model. The Quality Assessment of Diagnostic Accuracy Studies‐2 tool was used for the quality assessment. A total of 27 studies involving 6960 patients were included in our study. The summary sensitivity of early imaging studies was 0.95 (95% CI, 0.79–0.99), and the specificity was 0.89 (95% CI, 0.85–0.92). The positive posterior probability was 19.11%, and the negative posterior probability was 0.16%. The summary sensitivity of delayed imaging studies was 0.98 (95% CI, 0.92–1.00), and the specificity was 1.00 (95% CI, 0.98–1.00). The positive posterior probability was 95.76%, and the negative posterior probability was 0.12%. The delayed imaging method significantly improved the specificity (1.00 versus 0.89; P <0.05) and positive posterior probability (95.76% versus 19.11%; P <0.05). Conclusions Cardiac computed tomography with a delayed imaging is a reliable alternative to TEE. It may save the patient and health care from an excess TEE. Registration URL: https://www.crd.york.ac.uk/PROSPERO ; Unique identifier: CRD42021236352.

Delayed FDG PET Provides Superior Glioblastoma Conspicuity Compared to Conventional Image Timing

Background: Glioblastomas are malignant, often incurable brain tumors. Reliable discrimination between recurrent disease and treatment changes is a significant challenge. Prior work has suggested glioblastoma FDG PET conspicuity is improved at delayed time points vs. conventional imaging times. This study aimed to determine the ideal FDG imaging time point in a population of untreated glioblastomas in preparation for future trials involving the non-invasive assessment of true progression vs. pseudoprogression in glioblastoma.Methods: Sixteen pre-treatment adults with suspected glioblastoma received FDG PET at 1, 5, and 8 h post-FDG injection within the 3 days prior to surgery. Maximum standard uptake values were measured at each timepoint for the central enhancing component of the lesion and the contralateral normal-appearing brain.Results: Sixteen patients (nine male) had pathology confirmed IDH-wildtype, glioblastoma. Our results revealed statistically significant improvements in the maximum standardized uptake values and subjective conspicuity of glioblastomas at later time points compared to the conventional (1 h time point). The tumor to background ratio at 1, 5, and 8 h was 1.4 ± 0.4, 1.8 ± 0.5, and 2.1 ± 0.6, respectively. This was statistically significant for the 5 h time point over the 1 h time point (p &gt; 0.001), the 8 h time point over the 1 h time point (p = 0.026), and the 8 h time point over the 5 h time point (p = 0.036).Conclusions: Our findings demonstrate that delayed imaging time point provides superior conspicuity of glioblastoma compared to conventional imaging. Further research based on these results may translate into improvements in the determination of true progression from pseudoprogression.

Results of a Prospective Trial to Compare 68Ga-DOTA-TATE with SiPM-Based PET/CT vs. Conventional PET/CT in Patients with Neuroendocrine Tumors

We prospectively enrolled patients with neuroendocrine tumors (NETs). They underwent a single 68Ga-DOTA-TATE injection followed by dual imaging and were randomly scanned using first either the conventional or the silicon photomultiplier (SiPM) positron emission tomography/computed tomography (PET/CT), followed by imaging using the other system. A total of 94 patients, 44 men and 50 women, between 35 and 91 years old (mean ± SD: 63 ± 11.2), were enrolled. Fifty-two out of ninety-four participants underwent SiPM PET/CT first and a total of 162 lesions were detected using both scanners. Forty-two out of ninety-four participants underwent conventional PET/CT first and a total of 108 lesions were detected using both scanners. Regardless of whether SiPM-based PET/CT was used first or second, maximum standardized uptake value (SUVmax) of lesions measured on SiPM was on average 20% higher when comparing two scanners with all enrolled patients, and the difference was statistically significant. SiPM-based PET/CT detected 19 more lesions in 13 patients compared with conventional PET/CT. No lesions were only identified by conventional PET/CT. In conclusion, we observed higher SUVmax for lesions measured from SiPM PET/CT compared with conventional PET/CT regardless of the order of the scans. SiPM PET/CT allowed for identification of more lesions than conventional PET/CT. While delayed imaging can lead to higher SUVmax in cancer lesions, in the series of lesions identified when SiPM PET/CT was used first, this was not the case; therefore, the data suggest superior performance of the SiPM PET/CT scanner in visualizing and quantifying lesions.

A bioactivated in vivo assembly (BIVA) nanotechnology fabricated NIR probe for small pancreatic tumor intraoperative navigation imaging

Visual intraoperative navigation depends on the optical technique for real-time imaging of the boundary of tumor. However, the fluorescence probes now enable for bioimaging are usually lack of tumor specificity and poor imaging window, which limited the further clinical applications. Here, we report a bioactivated in vivo assembly (BIVA) nanotechnology, which provides a universal optical probe delivery system to enhance the targeting specificity, region accumulation and continuous imaging window of the probe. Based on the coupling of BIVA domain and probe, BIVA probe exhibits a synergy mechanism of active targeting and assembly induced retention, which improved the targeting efficiency. In addition, the tumor surface specific nanofiber assembly significantly increases the accumulation of the probe at tumor boundary. The PEGylation of the BIVA probe extended the blood circulation time for 110 min, and the area under the curve (AUC 0-120 h) of tumor was significantly increased by 3.6 times compared with the active targeting probe. As the dynamic assembly difference between tumor and background further enlarges the metabolic difference, we obtained a delayed imaging window between 8-96 hours with better signal-to-background ratio (SBR > 9 times). Our BIVA probe can be used for imaging of small-size (d < 2 mm) orthotopic pancreatic tumors in vivo. The high specificity and sensitivity of the BIVA probe will further benefit the intraoperative navigation imaging in clinical.

ICAM-1-Carrying Targeted Nano Contrast Agent for Evaluating Inflammatory Injury in Rabbits with Atherosclerosis

Purpose To investigate the feasibility of using ICAM-1-carrying targeted nano ultrasonic contrast to evaluate the degree of inflammatory injury at different stages in the abdominal aorta of rabbits with atherosclerosis (AS). Methods Twenty-five experimental rabbits were assigned to five groups: the preoperative control group (A); the week-4 after modeling group(B); the week-8 after modeling group(C); the week-12 after modeling group(D); the week-16 after modeling group(E). All groups were given 2D ultrasonography, conventional ultrasonic contrast (SonoVue), and ICAM-1-carrying targeted nano ultrasonic contrast, respectively. Contrast parameters, including the peak intensity (PI), time to peak (TTP), and area under curve (AUC) of the region of interest, were used to evaluate the characteristics of vascular perfusion contrast. Results ICAM-1-carrying targeted nano ultrasonic contrast showed that the intensity of targeted micro-signals in the vascular wall of the abdominal bubble aorta gradually increased in B, C, D, and E groups (all P < 0.05). A positive linear correlation between PI and AUC and the expression of ICAM-1 (r = 0.893, P < 0.001; r = 0.934, P < 0.001). In ICAM-1-carrying targeted nano ultrasonic contrast, delayed imaging of the vascular wall of the abdominal aorta was observed, the outer membrane was thickened from week 4 to week 12, and both the intima-media membrane and outer membrane were thickened and with double-layer parallel echo at week 16, which was in line with the progression of atherosclerotic plaque vulnerability. Conclusion ICAM-1-carrying targeted nano contrast agent could evaluate the degree of inflammatory injury related to atherosclerotic progression and site high expression of specific adhesion molecules in early atherosclerotic lesions.

Predicting long-term outcomes in acute intracerebral haemorrhage using delayed prognostication scores

ObjectiveThe concept of the ‘self-fulfilling prophecy’ is well established in intracerebral haemorrhage (ICH). The ability to improve prognostication and prediction of long-term outcomes during the first days of hospitalisation is important in guiding conversations around goals of care. We previously demonstrated that incorporating delayed imaging into various prognostication scores for ICH improves the predictive accuracy of 90-day mortality. However, delayed prognostication scores have not been used to predict long-term functional outcomes beyond 90 days.Design, setting and participantsWe analysed data from the ICH Deferoxamine trial to see if delaying the use of prognostication scores to 96 hours after ICH onset will improve performance to predict outcomes at 180 days. 276 patients were included.Interventions and measurementsWe calculated the original ICH score (oICH), modified-ICH score (MICH), max-ICH score and the FUNC score on presentation (baseline), and on day 4 (delayed). Outcomes assessed were mortality and poor functional outcome in survivors (defined as modified Rankin Scale of 4–5) at 180 days. We generated receiver operating characteristic curves, and measured the area under the curve values (AUC) for mortality and functional outcome. We compared baseline and delayed AUCs with non-parametric methods.ResultsAt 180 days, 21 of 276 (7.6%) died. Out of the survivors, 54 of 255 had poor functional outcome (21.2%). The oICH, MICH and max-ICH performed significantly better at predicting 180-day mortality when calculated 4 days later compared with their baseline equivalents ((0.74 vs 0.83, p=0.005), (0.73 vs 0.80, p=0.036), (0.74 vs 0.83, p=0.008), respectively). The delayed calculation of these scores did not significantly improve our accuracy for predicting poor functional outcomes.ConclusionDelaying the calculation of prognostication scores in acute ICH until day 4 improved prediction of 6-month mortality but not functional outcomes.Trial registration numberClinicalTrials.gov Registry (NCT02175225).

66Ga-PET-imaging of GRPR-expression in prostate cancer: production and characterization of [66Ga]Ga-NOTA-PEG2-RM26

Molecular imaging of the gastrin-releasing peptide receptor (GRPR) could improve patient management in prostate cancer. This study aimed to produce gallium-66 (T½ = 9.5 h) suitable for radiolabeling, and investigate the imaging properties of gallium-66 labeled GRPR-antagonist NOTA-PEG2-RM26 for later-time point PET-imaging of GRPR expression. Gallium-66 was cyclotron-produced using a liquid target, and enriched [66Zn]Zn(NO3)2. In vitro, [66Ga]Ga-NOTA-PEG2-RM26 was characterized in GRPR-expressing PC-3 prostate cancer cells. In vivo, specificity test and biodistribution studies were performed 3 h and 22 h pi in PC-3 xenografted mice. microPET/MR was performed 3 h and 22 h pi. Biodistribution of [66Ga]Ga-NOTA-PEG2-RM26 was compared with [68Ga]Ga-NOTA-PEG2-RM26 3 h pi. [66Ga]Ga-NOTA-PEG2-RM26 was successfully prepared with preserved binding specificity and high affinity towards GRPR. [66Ga]Ga-NOTA-PEG2-RM26 cleared rapidly from blood via kidneys. Tumor uptake was GRPR-specific and exceeded normal organ uptake. Normal tissue clearance was limited, resulting in no improvement of tumor-to-organ ratios with time. Tumors could be clearly visualized using microPET/MR. Gallium-66 was successfully produced and [66Ga]Ga-NOTA-PEG2-RM26 was able to clearly visualize GRPR-expression both shortly after injection and on the next day using PET. However, delayed imaging did not improve contrast for Ga-labeled NOTA-PEG2-RM26.