Post-injection Time Research Articles

18F]PI-2620 Tau PET signal across the aging and Alzheimer’s disease clinical spectrum

Abstract [18F]PI-2620 is a second generation tracer that has shown high binding affinity for tau aggregation in Alzheimer’s disease (AD). However, [18F]PI-2620 signal in a large sample spanning the healthy aging and AD clinical spectrum as well as the stability of signal across different acquisition time windows have not yet been examined. Here, amyloid negative (Aβ-) cognitively unimpaired (CU; n=49), amyloid positive (Aβ+) CU (n=37), CU individuals with unknown amyloid status (n=5), mild cognitive impairment (MCI; n=14), dementia due to AD (n=19), and non-AD neurodegenerative disorder (n=54) participants were scanned with [18F]PI-2620 using a 45-75 min and/or 60-90 min acquisition time window. The impact of acquisition time on standardized uptake value ratio (SUVR) magnitude was first quantified with linear mixed models and in participants and regions with high [18F]PI-2620 signal, SUVRs increased linearly up to 0.04 SUVR with each additional 5 min past injection time. We then accounted for differences in acquisition time using a voxelwise correction approach and showed high correlations (all rs>0.986) between SUVRs calculated from 45-75 min data and SUVRs from 60-90 min data that were interpolated to the 45-75 min scale in 15 participants who were scanned across both time windows. Using real and interpolated 45-75 min data, we next examined [18F]PI-2620 signal in Braak regions of interest and an off-target binding region (putamen) in Aβ- and Aβ+ CU, Aβ+ MCI, and Aβ+ AD dementia (n=115) and showed that SUVRs in all Braak regions increased with greater disease severity. Within CU, higher Braak I SUVR was significantly associated with greater CSF pTau-181 (n=35), and higher SUVRs were significantly associated with worse memory and language (n=57). Thus, voxelwise acquisition time corrections can be applied to combine [18F]PI-2620 datasets collected at different post-injection times, and once acquisition time is accounted for, [18F]PI-2620 signal shows the expected increases across the AD spectrum and can be used for detection of early tau elevations.

Localization and Tumor Growth Inhibition of I-131-Labeled Monoclonal Antibody ERIC1 in a Subcutaneous Xenograft Model of Small Cell Lung Cancer in SCID Mice.

This study evaluates the efficacy of [131I]I-ERIC1 in targeting and inhibiting the growth of SCLC tumors in mice, focusing on tumor accumulation and regression and potential side effects. NCAM-positive NCI-H69 SCLC cells were implanted in CB 17 SCID mice, and [131I]I-ERIC1 biokinetics were measured in organs and tissues at four post-injection time points (24, 72, 96, and 120 h). The experimental series compared tumor growth, survival, and changes in blood counts among three treatment groups (1, 2, or 3 MBq) and a control group, with treatments initiated either two or five days post implantation. [131I]I-ERIC1 was synthesized with >95% radiochemical purity and a specific activity of 15 TBq/mmol. Tumor activity peaked at 31.5 ± 6.6% ID/g after four days, demonstrating significant antitumor efficacy, which resulted in sustained remission and extended survival. Hematological toxicity was observed, with the optimal dose identified as 2 MBq per animal administered two days post implantation. [131I]I-ERIC1 shows promise as a theranostic agent for personalized cancer treatment by effectively targeting SCLC tumors with manageable side effects. However, further studies are required to optimize dosing strategies and minimize toxicity.

Magnetic Resonance Imaging of Fibroblast Activation Protein Using a Targeted Gadolinium-Based Contrast Agent.

The aim of this study was to synthesize a quinoline-based MRI contrast agent, Gd-DOTA-FAPI04, and assess its capacity for targeting fibroblast activation protein (FAP)-positive tumors in vivo. Gd-DOTA-FAPI04 was synthesized by attaching a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complex of gadolinium(III) to FAP inhibitor FAPI04. The longitudinal relaxation time (T1) of the contrast agent was measured using a Siemens Prisma 3.0T MR system, and the CCK-8 assay was performed to evaluate its potential cytotoxicity. Male nude mice bearing tumors grown from FAP-expressing fibrosarcoma cells were divided into experimental (n = 4) and control (n = 4) groups, and T1-weighted image enhancement was measured at different times (0, 10, 30, 60, 90, and 120 min) postinjection of Gd-DOTA-FAPI04. The control group received an additional preinjection of excess FAPI04. FAP expression in tumor tissue was investigated by using immunohistochemistry with an anti-FAP antibody. The longitudinal relaxivities of gadodiamide and Gd-DOTA-FAPI04 were measured to be 3.734 mM-1 s-1 and 5.323 mM-1 s-1, respectively. The CCK-8 assay demonstrated that Gd-DOTA-FAPI04 has minimal toxicity to cultured human fibrosarcoma cells. In vivo MRI showed that peak accumulation of Gd-DOTA-FAPI04 in FAP-expressing tumors occurred 1 h postinjection and could be blocked by preinjection of excess FAPI04. Immunohistochemical analysis of harvested tumor tissue supported the above findings. Gd-DOTA-FAPI04 is a promising contrast agent for in vivo imaging of FAP.

Florbetaben amyloid PET acquisition time: Influence on Centiloids and interpretation.

Amyloid positron emission tomography (PET) acquisition timing impacts quantification. In florbetaben (FBB) PET scans of 245 adults with and without cognitive impairment, we investigated the impact of post-injection acquisition time on Centiloids (CLs) across five reference regions. CL equations for FBB were derived using standard methods, using FBB data collected between 90 and 110 min with paired Pittsburgh compound B data. Linear mixed models and t-tests evaluated the impact of acquisition time on CL increases. CL values increased significantly over the scan using the whole cerebellum, cerebellar gray matter, and brainstem as reference regions, particularly in amyloid-positive individuals. In contrast, CLs based on white matter-containing reference regions decreased across the scan. The quantification of CLs in FBB PET imaging is influenced by both the overall scan acquisition time and the choice of reference region. Standardized acquisition protocols or the application of acquisition time-specific CL equations should be implemented in clinical protocols. Acquisition timing affects florbetaben positron emission tomography (PET) scan quantification, especially in amyloid-positive participants. The impact of acquisition timing on quantification varies across common reference regions. Consistent acquisitions and/or appropriate post-injection adjustments are needed to ensure comparability of PET data.

Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy

BackgroundUnderstanding the mechanism behind sepsis-associated encephalopathy (SAE) remains a formidable task. This study endeavors to shed light on the complex cellular and molecular alterations that occur in the brains of a mouse model with SAE, ultimately unraveling the underlying mechanisms of this condition.MethodsWe established a murine model using intraperitoneal injection of lipopolysaccharide (LPS) in wild type and Anxa1−/− mice and collected brain tissues for analysis at 0-hour, 12-hour, 24-hour, and 72-hour post-injection. Utilizing advanced techniques such as single-nucleus RNA sequencing (snRNA-seq) and Stereo-seq, we conducted a comprehensive characterization of the cellular responses and molecular patterns within the brain.ResultsOur study uncovered notable temporal differences in the response to LPS challenge between Anxa1−/− (annexin A1 knockout) and wild type mice, specifically at the 12-hour and 24-hour time points following injection. We observed a significant increase in the proportion of Astro-2 and Micro-2 cells in these mice. These cells exhibited a colocalization pattern with the vascular subtype Vas-1, forming a distinct region known as V1A2M2, where Astro-2 and Micro-2 cells surrounded Vas-1. Moreover, through further analysis, we discovered significant upregulation of ligands and receptors such as Timp1-Cd63, Timp1-Itgb1, Timp1-Lrp1, as well as Ccl2-Ackr1 and Cxcl2-Ackr1 within this region. In addition, we observed a notable increase in the expression of Cd14-Itgb1, Cd14-Tlr2, and Cd14-C3ar1 in regions enriched with Micro-2 cells. Additionally, Cxcl10-Sdc4 showed broad upregulation in brain regions containing both Micro-2 and Astro-2 cells. Notably, upon LPS challenge, there was an observed increase in Anxa1 expression in the mouse brain. Furthermore, our study revealed a noteworthy increase in mortality rates following Anxa1 knockdown. However, we did not observe substantial differences in the types, numbers, or distribution of other brain cells between Anxa1−/− and wildtype mice over time. Nevertheless, when comparing the 24-hour post LPS injection time point, we observed a significant decrease in the proportion and distribution of Micro-2 and Astro-2 cells in the vicinity of blood vessels in Anxa1−/− mice. Additionally, we noted reduced expression levels of several ligand-receptor pairs including Cd14-Tlr2, Cd14-C3ar1, Cd14-Itgb1, Cxcl10-Sdc4, Ccl2-Ackr1, and Cxcl2-Ackr1.ConclusionsBy combining snRNA-seq and Stereo-seq techniques, our study successfully identified a distinctive cellular colocalization, referred to as a special pathological niche, comprising Astro-2, Micro-2, and Vas-1 cells. Furthermore, we observed an upregulation of ligand-receptor pairs within this niche. These findings suggest a potential association between this cellular arrangement and the underlying mechanisms contributing to SAE or the increased mortality observed in Anxa1 knockdown mice.

Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma

ObjectivesTo evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard.MethodsThis retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015–2021). SER is defined as (SIlt − SIpre)/(SIea − SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan–Meier curves.ResultsThe internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29–0.74, all p < 0.001) and epithelium (r = −0.23 to −0.71, all p < 0.001) across a wide post-injection time window (range, 25–300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17–2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25–2.41), p = 0.001).ConclusionSER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC.Clinical relevance statementThe signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC.Key PointsImaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma.Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers.Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.Graphical

A Comparison of Analgesic Efficacy of Triamcinolone vs Magnesium Sulfate as Adjuvants in Caudal Block in Patients with Low Back Pain: A Double-Blind Randomized Controlled Trial.

Chronic low back pain (CLBP) is a common issue among older adults. Radicular pain syndromes are often managed with caudal epidural injections. Our study aimed to compare the effects of triamcinolone and magnesium sulfate, used as adjuvants to local anesthetics in caudal blocks, on pain levels and quality of life in patients with LBP. A total of 40 patients undergoing caudal block were randomized to two groups,received 10 mL caudal epidural injection of either injection 9 mL of ropivacaine 0.1% and 1 mL of triamcinolone; 40 mg (Group T, n = 20) or magnesium sulfate; 200 mg (group M, n = 20). Improvements in the pain score measured with the Visual Analog Scale (VAS) and functional ability measured with the Oswestry Disability Index (ODI) were the primary and secondary outcome measures, respectively. Before, one month and three months after the caudl block, the VAS and ODI scores were evaluated. The VAS and ODI scores did not exhibit a significant difference between the 2 groups at all post-injection time points, except for the VAS score at 3 months, which showed a statistically lower value in group M compared to group T (P = 0.046). However, when comparing within the same group, both groups showed significantly improved VAS and ODI scores at all post-injection time points compared to the pre-injection scores (P < 0.0001). The addition of magnesium or triamcinolone to a local anesthetic in caudal epidural injections does not result in any discernible difference. However, this combination may lead to improvements in pain levels and quality of life, and these improvements can be sustained for up to 3 months.

Test-Retest Repeatability of Patlak Slopes versus Standardized Uptake Values for Hypermetabolic Lesions and Normal Organs in an Oncologic PET/CT Population.

We aimed to determine the test-retest repeatability of quantitative metrics based on the Patlak slope (PS) versus the standardized uptake value (SUV) among lesions and normal organs on oncologic [18F]FDG-PET/CT. This prospective, single-center study enrolled adults undergoing standard-of-care oncologic [18F]FDG-PET/CTs. Early (35-50min post-injection) and late (75-90min post-injection) SUV and PS images were reconstructed from dynamic whole-body PET data. Repeat imaging occurred within 7days. Relevant quantitative metrics were extracted from lesions and normal organs. Repeatability was assessed via mean test-retest percent changes [T-RT %Δ], within-subject coefficients of variation (wCVs), and intra-class correlation coefficients (ICCs). Nine subjects (mean age, 61.7 ± 6.2years; 6 females) completed the test-retest protocol. Four subjects collectively had 17 [18F]FDG-avid lesions. Lesion wCVs were higher (i.e., worse repeatability) for PS-early-max (16.2%) and PS-early-peak (15.6%) than for SUV-early-max (8.9%) and SUV-early-peak (8.1%), with similar early metric ICCs (0.95-0.98). Lesion wCVs were similar for PS-late-max (8.5%) and PS-late-peak (6.4%) relative to SUV-late-max (9.7%) and SUV-late-peak (7.2%), with similar late metric ICCs (0.93-0.98). There was a significant bias toward higher retest SUV and PS values in the lesion analysis (T-RT %Δ [95% CI]: SUV-late-max, 10.0% [2.6%, 17.0%]; PS-late-max, 20.4% [14.3%, 26.4%]) but not in the normal organ analysis. Among [18F]FDG-avid lesions, the repeatability of PS-based metrics is similar to equivalent SUV-based metrics at late post-injection time points, indicating that PS-based metrics may be suitable for tracking response to oncologic therapies. However, further validation is required in light of our study's limitations, including small sample size and bias toward higher retest values for some metrics.

Intratympanic injections of emulsion-like dispersions to augment cinnarizine amount in a healthy rabbit inner ear model.

Aim: To investigate eutectic liquid-based emulsion-like dispersions for intratympanic injections to augment cinnarizine permeability across round window membrane in a healthy rabbit inner ear model.Methods: Two-tier systematic optimization was used to get the injection formula. The drug concentrations in perilymph and plasma were analyzed via. Ultra-performance liquid chromatography-tandem mass spectrometry method after 30-, 60-, 90- and 120-min post intratympanic injection time points in rabbits.Results: A shear-thinning behavior, immediate drug release (∼98.80%, 10min) and higher cell viability (>97.86%, 24h) were observed in dispersions. The cinnarizine level of 8168.57±1236.79ng/ml was observed in perilymph at 30min post intratympanic injection in rabbits.Conclusion: The emulsion-like dispersions can augment drug permeability through round window membrane.

Thermal management strategy for active regeneration of diesel particulate filter

The method of diesel oxidation catalyst (DOC) assistance is an effective way to achieve active regeneration of diesel particulate filter (DPF). Therefore, an appropriate DOC inlet temperature is the essential boundary condition for this regeneration process. In this paper, the thermal management measures and a novel strategy based on the requirements of DPF active regeneration have been proposed and studied through experiments. Results show that intake throttling can increase DOC inlet temperature by 45% at high speed and 13% at low speed. However, its effect becomes significant only after the throttle closure exceeds 65%. Near post-injection is a more effective method than intake throttling to increase the DOC inlet temperature, and is suitable for situations where the DOC inlet temperature differs greatly from the target value. Under the premise of economic consideration, the optimal value of near post-injection time is always 20°CA after top dead center (TDC). The near post-injection quantity has a greater effect on DOC inlet temperature than the near post-injection time. However, too large near post-injection quantity can also lead to a sharp deterioration in fuel economy. Meanwhile, a novel thermal management strategy based on engine working zone division is proposed according to the ability of different thermal management measures and the distribution law of original DOC inlet temperature. With this strategy, the DOC inlet temperature in whole engine operating range increases significantly. In steady state, more than 80% of the operating points can reach the target value of 450 ℃. In world harmonized transient cycle (WHTC), the average DOC inlet temperature is also increased by 28.8%.

Contrast administration via ultrasound-guided injection of the cranial tibial artery results in contrast enhancement of the soft tissues of the metatarsus in horses undergoing CT.

Delivery of mesenchymal stem cells (MSC) via intravascular techniques to treat diffuse and/or inaccessible soft tissue injuries has grown in popularity. The purpose of the current prospective, analytical pilot study was to utilize CT to validate this novel technique and provide additional evidence to support its use for injectate delivery to specific soft tissue structures. Of particular interest was the proximal suspensory ligament, which presents a challenging injection target. Six adult horses without lameness underwent CT of the distal hindlimbs. Scans were obtained prior to ultrasound-guided catheterization of the cranial tibial artery, in addition to early and delayed scans acquired following intra-arterial contrast administration. Region of interest analysis of the superficial and deep digital flexor tendons and suspensory ligament was used to assess contrast enhancement within these structures. Linear mixed models were used to determine statistical significance. Significant (P<0.05) mean contrast enhancement was seen in all postinjection time points in all soft tissue structures of interest. This indicates that ultrasound-guided injection of the cranial tibial artery results in perfusion of injectate throughout the distal hind limb, including the major soft tissue structures of the metatarsus. This provides further support for this technique as a method of MSC delivery to multifocal or inaccessible injury of these structures, including the proximal suspensory ligament.

Analgesic efficacy and functional outcome in refractory cases of plantar fasciitis treated with platelet-rich plasma: randomized comparative study with corticosteroids injection

ABSTRACT Background Steroid injection is a widespread treatment for plantar fasciitis but seems to be useful to a lesser extent, Platelet-rich Plasma (PRP) injections into the plantar fascia start the healing process required to stop the degeneration of the plantar fascia at its root. Aim of the study To compare analgesic efficacy, functional outcome, degree of satisfaction and improvement of fascial thickness and echogenicity after platelet-rich plasma injection versus corticosteroids injection in refractory cases of plantar fasciitis. Patients & method 60 patients with refractory plantar fasciitis who were resistant to conservative treatment were randomized to receive either PRP or steroid injection. All patients were assessed with the American Orthopaedic Foot and Ankle Society (AOFAS) score, Visual Analogue Score (VAS) for pain, the Roles-Maudsley (RM) Score and plantar fascia thickness and echogenicity. Data were collected prospectively, pre-treatment, at 3, 6, 12 week, and 6 months post-injection. Results There was significant improvement in both groups as regards the clinical outcome measures involving (VAS & AOFAS) and radiological outcome measures including (thickness and echogenicity) in all post-injection times. However, steroid group showed early improvement (at 3rd week post-injection) with short duration while PRP group showed improvement at 12 weeks post-injection till the end of the study. Conclusion The use of PRP injection is safer with better analgesia and functional outcome than steroid therapy for treating chronic plantar fasciitis.

Evaluation of single-delay arterial spin labeling-based spatial coefficient of variation and histogram-based parameters in relation to cerebrovascular reserve in patients with Moyamoya disease.

Single-delay Arterial Spin Labeling (ASL)-based spatial coefficient of variation (CoVCBF) has been suggested as a measure of hemodynamic disturbance in patients with cerebrovascular diseases. However, spatial CoVCBF and other histogram-based parameters such as skewness and kurtosis and the volume of the arterial transit time artefact (ATAvol), has not been evaluated in patients with MMD nor against cerebrovascular reserve (CVR). The aim of this study was to assess whether any associations between spatial CoVCBF, skewness, kurtosis, and ATAvol are present and to analyze any potential associations with CVR, derived from single-delay ASL in patients with MMD. Fifteen MMD patients were included before or after revascularization surgery. Cerebral blood flow (CBF) maps were acquired using pseudo-continuous ASL before, and 5, 15, and 25 min after an intravenous acetazolamide injection. CVRmax was defined as the highest percentual increase in CBF at any of the three post-injection time points. A vascular territory template was spatially normalized to each patient, including the bilateral anterior, middle, and posterior cerebral arteries. All affected anterior and middle cerebral artery regions and all unaffected posterior cerebral artery regions were included, based on Suzuki grading by digital subtraction angiography. Significant differences between affected and unaffected regions were found for CBF, CVRmax, and ATAvol. No association was found between CVRmax and any other parameter. High correlations were found between spatial CoVCBF, skewness and ATAvol. Spatial CoVCBF derived from single-delay ASL does not correlate with CVR in patients with MMD. Moreover, skewness and kurtosis did not provide additional information of clinical value.

Metabolic and osmoionic effects of the recombinant crustacean hyperglycemic hormone (rCHH-A) of the Pacific white shrimp Penaeus vannamei on specimens acutely exposed to extreme salinities

The crustacean hyperglycemic hormone (CHH) is a multifunctional neuropeptide that plays a central role in crustacean metabolism and physiology. Experiments were conducted to examine the metabolic and osmoionic capabilities of the white shrimp Penaeus vannamei injected with its recombinant CHH-A (rCHH-A) peptide and acutely transferred from iso- (26 ppt) to hypo- (10 ppt) and hyper-osmotic (40 ppt) conditions. Hemolymph glucose, protein, osmoregulatory capacity (OC), and ionoregulatory capacity (IC) for sodium, chloride, potassium, and calcium were evaluated at four post-injection times (0.5, 1, 2, and 24 h). The rCHH-A peptide had hyperglycemic activity in all salinity conditions, obtaining maximum values at 1 h post-injection. However, in shrimp transferred to hyper-osmotic condition, rCHH-A caused the most significant reductions in OC (2 h), chloride IC (2 h), and total proteins (0.5-2 h) compared to the phosphate-buffered saline (PBS) control. Contrastingly, in shrimp transferred to hypo-osmotic conditions, rCHH-A decreased OC significantly from 2-24 h, strongly decreased chloride and potassium IC at 1 h post-injection, and increased total protein concentration in the hemolymph (1-2 h) when compared to PBS control. Concerning calcium, the rCHH-A injection decreased calcium IC at 10 ppt (1 h) and 26 ppt (2 h), providing insight into a potential role for CHH-A in calcium regulation. The results suggest that glucose and protein mobilization could enhance energy for osmo-ionic regulation under extreme osmotic conditions. This research study contributed to understanding crustacean endocrinology in P. vannamei and related euryhaline crustaceans. Further research should be performed to understand the osmo- and ionoregulatory mechanisms of the different CHH variants in crustaceans exposed to other stress conditions and the relationship with intermediary energy metabolism regulation.

Impact of uptake time on image quality of [68 Ga]Ga-PSMA-11 PET/CT.

With the introduction of prostate specific membrane antigen (PSMA) PET/CT, the detection rate of prostate cancer metastases has improved significantly, both for primary staging and for biochemical recurrence. EANM/SNMMI guidelines recommend a 60min time interval between [68 Ga]Ga-PSMA administration and acquisition. This study evaluates the possibility of a shorter time interval by investigating the dynamic change in image quality measures. We retrospectively analyzed 10 consecutive prostate cancer patients who underwent a dynamic whole body [68 Ga]Ga-PSMA-11 PET/CT of 75min from skull vertex to mid-thigh using Siemens FlowMotion. PET images were acquired directly after injection of 1.5MBq/kg [68 Ga]Ga-PSMA-11. Image quality measures included lesion maximum standardized uptake value corrected for lean body mass (SULmax ), tumor-to-background ratio (TBR), and contrast-to-noise ratio (CNR). Quantitative analysis of image quality in dynamic PET was performed using PMOD (version 4.2). Regions of interest (ROIs), drawn included different types of prostate lesions (primary tumor, lymph nodes, and bone metastasis), organ tissue (liver, spleen, lacrimal gland, submandibular gland, parotid gland, urinary bladder, kidneys blood pool [ascending aorta], left ventricle), bone tissue (4th lumbar vertebral body [L4]) and muscle tissue (gluteus maximus). To further investigate image quality four 10min multi-frame reconstructions with clinical parameters were made at different post-injection times (15, 30, 45, and 60min). A nuclear medicine physician performed a blinded lesion detectability evaluation on these multi-frame reconstructions for different prostate cancer lesions. Six primary prostate tumors in seven patients with prostate in situ, 13 lymph node metastases in six patients and up to 12 bone metastases in three patients were found. The different prostate lesion types (lymph nodes metastases, bone metastases, and primary prostate tumor) all show an increase in average SULmax , TBR, and CNR over time during the scan. The normalized average SULmax , TBR, and CNR of the combined prostate lesions at 15, 30, and 45min post-injection scans were all significant p<0.05 lower from the 60min post-injection [68 Ga]Ga-PSMA-11 PET/CT (9.5±4.5, 12.7±6.2, and 41.8±24.5, respectively). At patient level, the reader concluded the same regarding the presence/absence of primary prostate cancer recurrence, lymph node metastases, and/or bone metastases on all <60min post-injection [68 Ga]Ga-PSMA-11 PET/CT's in comparison to the reference scan (60min post-injection). At lesion level, all bone metastases seen on the reference scan were also seen on all <60min post-injection [68 Ga]Ga-PSMA-11 PET/CT's but there were some lymph nodes (n=2) metastases missed on the 15, 30, and 45min post-injection scans. One lymph node metastasis on both the 15 and 30min post-injection [68 Ga]Ga-PSMA-11 PET/CT's was missed and one lymph node metastasis was missed, only on the 45min post-injection [68 Ga]Ga-PSMA-11 PET/CT. Shorter post-injection times (15, 30, and 45min) compared to the recommended post-injection time of 60min are not optimal. However, the impact of a shorter time interval of 45min instead of 60min between [68 Ga]Ga-PSMA-11 administration and the start of PET/CT acquisition on both image quality (SULmax , TBR, and CNR) and lesion detection, while significant, is small.

Reduction of Gadolinium-Based Contrast Agents in MRI Using Convolutional Neural Networks and Different Input Protocols: Limited Interchangeability of Synthesized Sequences With Original Full-Dose Images Despite Excellent Quantitative Performance.

The purpose of this study was to implement a state-of-the-art convolutional neural network used to synthesize artificial T1-weighted (T1w) full-dose images from corresponding noncontrast and low-dose images (using various settings of input sequences) and test its performance on a patient population acquired prospectively. In this monocentric, institutional review board-approved study, a total of 138 participants were included who received an adapted imaging protocol with acquisition of a T1w low dose after administration of 10% of the standard dose and acquisition of a T1w full dose after administration of the remaining 90% of the standard dose of a gadolinium-containing contrast agent. A total of 83 participants formed the training sample (51.7 ± 16.5 years, 36 women), 25 the validation sample (55.3 ± 16.4 years, 11 women), and 30 the test sample (55.0 ± 15.0 years, 9 women). Four input settings were differentiated: only the T1w noncontrast and T1w low-dose images (standard setting), only the T1w noncontrast and T1w low-dose images with a prolonged postinjection time of 5 minutes (5-minute setting), multiple noncontrast sequences (T1w, T2w, diffusion) and the T1w low-dose images (extended setting), and only noncontrast sequences (T1w, T2w, diffusion) were used (zero-dose setting). For each setting, a deep neural network was trained to synthesize artificial T1w full-dose images, which were assessed on the test sample using an objective evaluation based on quantitative metrics and a subjective evaluation through a reader-based study. Three readers scored the overall image quality, the interchangeability in regard to the clinical conclusion compared with the true T1w full-dose sequence, the contrast enhancement of lesions, and their conformity to the respective references in the true T1w full dose. Quantitative analysis of the artificial T1w full-dose images of the standard setting provided a peak signal-to-noise ratio of 33.39 ± 0.62 (corresponding to an average improvement of the low-dose sequences of 5.2 dB) and a structural similarity index measure of 0.938 ± 0.005. In the 4-fold cross-validation, the extended setting yielded similar performance to the standard setting in terms of peak signal-to-noise ratio ( P = 0.20), but a slight improvement in structural similarity index measure ( P < 0.0001). For all settings, the reader study found comparable overall image quality between the original and artificial T1w full-dose images. The proportion of scans scored as fully or mostly interchangeable was 55%, 58%, 43%, and 3% and the average counts of false positives per case were 0.42 ± 0.83, 0.34 ± 0.71, 0.82 ± 1.15, and 2.00 ± 1.07 for the standard, 5-minute, extended, and zero-dose setting, respectively. Using a 5-point Likert scale (0 to 4, 0 being the worst), all settings of synthesized full-dose images showed significantly poorer contrast enhancement of lesions compared with the original full-dose sequence (difference of average degree of contrast enhancement-standard: -0.97 ± 0.83, P = <0.001; 5-minute: -0.93 ± 0.91, P = <0.001; extended: -0.96 ± 0.97, P = <0.001; zero-dose: -2.39 ± 1.14, P = <0.001). The average scores of conformity of the lesions compared with the original full-dose sequence were 2.25 ± 1.21, 2.22 ± 1.27, 2.24 ± 1.25, and 0.73 ± 0.93 for the standard, 5-minute, extended, and zero-dose setting, respectively. The tested deep learning algorithm for synthesis of artificial T1w full-dose sequences based on images after administration of only 10% of the standard dose of a gadolinium-based contrast agent showed very good quantitative performance. Despite good image quality in all settings, both false-negative and false-positive signals resulted in significantly limited interchangeability of the synthesized sequences with the original full-dose sequences.

Experimental and empirical analysis of performance, combustion and emission characteristics of diesel engine fueled with pyrolysis waste engine oil under single and split injection strategy

The present investigation studies the effects of single and split injection strategies on a diesel engine fuelled with diesel and microwave pyrolysis oil (MPO). MPO was extracted from waste engine oil (WEO) at 350–380 °C and utilized in a diesel engine after purification. The engine study was conducted using different nozzle opening pressures (NOP: 200 to 500 bar) and fuel injection timings (FIT: 17 to 27 oCA bTDC). Further, this work was extended to investigate the effect of a split injection strategy for MPO at 400 bar NOP under full load. In split injection, different split ratios, start of main injection time, and the start of post-injection time were studied. MPO's brake-specific energy consumption decreased by 7% at 400 bar NOP. NO and soot were 10% and 27% lower than diesel emissions at 400 bar NOP and bTDC 21 oCA FIT, respectively. Split injection strategy improved BTE by 1.4% and reduced NO and soot by 21% and 58% compared to the single injection strategy. The ANN model predicted the experimental results with a higher correlation coefficient (R) in the range of 0.98–0.99. Overall, the study inferred that the split injection strategy reduces exhaust emissions of MPO without affecting engine performance.

Case series profile of olanzapine post-injection delirium/sedation syndrome.

Olanzapine pamoate is an intramuscular depot injection for the treatment of schizophrenia. Approximately 1.4% of patients develop a serious adverse event called post-injection delirium/sedation syndrome (PDSS), characterised by drowsiness, anticholinergic and extrapyramidal symptoms. The objective is to investigate olanzapine PDSS presentations including clinical features and treatment approach. This is a retrospective review of olanzapine PDSS patients from three toxicology units and the NSW Poisons Information Centre between 2017 and 2022. Adult patients were included if they had intramuscular olanzapine then developed PDSS criteria. Clinical symptoms, treatment, timing and length of symptoms were extracted into a preformatted Excel database. There were 18 patients included in the series, with a median age of 49 years (interquartile range [IQR]: 38-58) and male predominance (89%). Median onset time post injection was 30 min (IQR: 11-38). PDSS symptoms predominate with drowsiness, confusion and dysarthria. Median length of symptoms was 24 h (IQR: 20-54). Most common treatment included supportive care without any pharmacological intervention (n = 10), benzodiazepine (n = 4) and benztropine (n = 3). In one case, bromocriptine and physostigmine followed by oral rivastigmine were given to manage antidopaminergic and anticholinergic symptoms respectively. This proposed treatment combination could potentially alleviate some of the symptoms but needs further studies to validate the findings. In conclusion, this case series supports the characterisation of PDSS symptomology predominantly being anticholinergic with similar onset (<1h) and duration (<72 h). Bromocriptine is proposed to manage PDSS if patients develop severe dopamine blockade and physostigmine followed by rivastigmine for anticholinergic delirium.

Tissue response curve-shape analysis of dynamic glucose-enhanced and dynamic contrast-enhanced magnetic resonance imaging in patients with brain tumor.

Dynamic glucose-enhanced (DGE) MRI is used to study the signal intensity time course (tissue response curve) after D-glucose injection. D-glucose has potential as a biodegradable alternative or complement to gadolinium-based contrast agents, with DGE being comparable with dynamic contrast-enhanced (DCE) MRI. However, the tissue uptake kinetics as well as the detection methods of DGE differ from DCE MRI, and it is relevant to compare these techniques in terms of spatiotemporal enhancement patterns. This study aims to develop a DGE analysis method based on tissue response curve shapes, and to investigate whether DGE MRI provides similar or complementary information to DCE MRI. Eleven patients with suspected gliomas were studied. Tissue response curves were measured for DGE and DCE MRI at 7 T and the area under the curve (AUC) was assessed. Seven types of response curve shapes were postulated and subsequently identified by deep learning to create color-coded "curve maps" showing the spatial distribution of different curve types. DGE AUC values were significantly higher in lesions than in normal tissue (p < 0.007). Furthermore, the distribution of curve types differed between lesions and normal tissue for both DGE and DCE. The DGE and DCE response curves in a 6-min postinjection time interval were classified as the same curve type in 20% of the lesion voxels, which increased to 29% when a 12-min DGE time interval was considered. While both DGE and DCE tissue response curve-shape analysis enabled differentiation of lesions from normal brain tissue in humans, their enhancements were neither temporally identical nor confined entirely to the same regions. Curve maps can provide accessible and intuitive information about the shape of DGE response curves, which is expected to be useful in the continued work towards the interpretation of DGE uptake curves in terms of D-glucose delivery, transport, and metabolism.

64Cu-/177Lu-Cetuximab Theranostic Pair: May the Single 64Cu-Cetuximab Diagnostic Scan Be Acquired at Any Time After Injection?

Two independent equations were recently proposed for estimating 177Lu-cetuximab cumulative activity, in a preclinical situation, from an initial 64Cu-cetuximab diagnostic scan acquired at peak time of decay-uncorrected (tpeak-uncorr) or decay-corrected (tpeak-corr) time-activity curve of trapped 64Cu-cetuximab, respectively. The standard uptake ratio (SUR) measured at tpeak-uncorr or tpeak-corr turned out to be a key metric in each equation, respectively. However, acquiring the diagnostic scan at tpeak-uncorr or tpeak-corr might be a limitation of the proposed method. Therefore, in an attempt to overcome this limitation, this note aims at theoretically investigating whether SUR(tpeak-uncorr) and/or SUR(tpeak-corr) could be derived from a diagnostic scan acquired at any time postinjection.