Mean Uptake Research Articles

Impacts of acquisition and reconstruction parameters on the absolute technetium quantification of the cadmium\u2013zinc\u2013telluride-based SPECT/CT system: a phantom study

BackgroundThe digital cadmium–zinc–telluride (CZT)-based SPECT system has many advantages, including better spatial and energy resolution. However, the impacts of different acquisition and reconstruction parameters on CZT SPECT quantification might still need to be validated. This study aimed to evaluate the impacts of acquisition parameters (the main energy window and acquisition time per frame) and reconstruction parameters (the number of iterations, subsets in iterative reconstruction, post-filter, and image correction methods) on the technetium quantification of CZT SPECT/CT.MethodsA phantom (PET NEMA/IEC image quality, USA) was filled with four target-to-background (T/B) ratios (32:1, 16:1, 8:1, and 4:1) of technetium. Mean uptake values (the calculated mean concentrations for spheres) were measured to evaluate the recovery coefficient (RC) changes under different acquisition and reconstruction parameters. The corresponding standard deviations of mean uptake values were also measured to evaluate the quantification error. Image quality was evaluated using the National Electrical Manufacturers Association (NEMA) NU 2–2012 standard.ResultsFor all T/B ratios, significant correlations were found between iterations and RCs (r = 0.62–0.96 for 1–35 iterations, r = 0.94–0.99 for 35–90 iterations) as well as between the full width at half maximum (FWHM) of the Gaussian filter and RCs (r = − 0.86 to − 1.00, all P values < 0.05). The regression coefficients of 1–35 iterations were higher than those of 35–90 iterations (0.51–1.60 vs. 0.02–0.19). RCs calculated with AC (attenuation correction) + SC (scatter correction) + RR (resolution recovery correction) combination were more accurate (53.82–106.70%) than those calculated with other combinations (all P values < 0.05). No significant statistical differences (all P values > 0.05) were found between the 15% and 20% energy windows except for the 32:1 T/B ratio (P value = 0.023) or between the 10 s/frame and 120 s/frame acquisition times except for the 4:1 T/B ratio (P value = 0.015) in terms of RCs.ConclusionsCZT-SPECT/CT of technetium resulted in good quantification accuracy. The favourable acquisition parameters might be a 15% energy window and 40 s/frame of acquisition time. The favourable reconstruction parameters might be 35 iterations, 20 subsets, the AC + SC + RR correction combination, and no filter.

Endoscopic treatment of primary vesicoureteral reflux in children with two different bulking agents, high success and low complication rates: Comparison of Dexell and Vantris

Introduction and objectivesTo compare the results in terms of efficacy and safety of the endoscopic management for vesicoureteral reflux (VUR) in two different standardized primary VUR cohorts treated with Dexell and Vantris. Patients128 refluxing renal units (RRU) in 87 patients with primary VUR (64 females, 23 males). Patients with secondary VUR and severe bladder and bowel dysfunction were excluded. A total of 22 continent children with mild bladder-bowel dysfunction underwent bladder-bowel training before the implantation. All procedures were performed in the presence of sterile urine using a conventional subureteral transurethral injection technique. ResultsThere were no statistically significant differences between groups in terms of mean age, sex, RRU side, 99mTc-DMSA uptake, and reflux grade. The overall resolution rates based on the number of RRUs for up to three endoscopic treatments were 80% (56/70) in Dexell group and 94.8% (55/58) in Vantris group (P = .012). No postoperative recurrences or vesicoureteral junction obstructions were seen in any group. ConclusionsDexell and Vantris provided an effective and safe endoscopic VUR treatment in the early and mid-term follow up of children with primary VUR. The effectiveness of these substances, which can produce different mass effects with different particle sizes, in safe VUR resolution, needs further investigations.

The Effects Of The Nike Vapor Fly 4% Shoes On Running Economy In Fatigued Female Runners

The Nike Vaporfly 4% shoe (VP) has been shown to improve running economy (RE) up to 4% in subelite male runners. Whether these improvements extend to other subject groups, such as female runners or fatigued runners, remains unknown. PURPOSE: The purpose of this study was to determine if trained female runners gain the same 4% improvement in RE as males and if the improvement is observed post-fatigue. METHODS: Nine well-trained collegiate female runners completed one session alternating between the VP and the control shoe, Nike Streaks (NS). Subjects performed three vertical jumps in each shoe on a force pad to determine jump height and estimate stored energy return from each shoe. Subjects then performed two, 5-min treadmill running trials at 6.7 mph using a metabolic cart to measure oxygen consumption. Mean oxygen uptake over the last two minutes of each trial was used to determine RE. Following the first jump and RE trials, subjects performed a 30-minute treadmill run at a self-selected speed to induce fatigue. Subjects then repeated the jump and RE trials in the alternative shoe order. RESULTS: Oxygen consumption in the VP was lower when compared to the NS by 3.7% (31.8 ± 3 vs 33.6 ± 3 ml/kg/min p < 0.05) pre-fatigue and by 2.5% (32.5 ± 3 vs 33.3 ± 3 ml/kg/min p < 0.05) in the fatigued state, which is less than the anticipated 4% benefit. The pre- and post-fatigue reductions in oxygen consumption while wearing the VP were significantly different indicating the benefit of wearing the VP attenuated over time. Jump height in the VP was higher pre-fatigue (44.0 ± 6 vs 43.2 ± 6 cm, p < 0.05) but was not different in the fatigued state (43.8 ± 7 vs 43.6 ± 7 cm, p > 0.05) when compared to NS. CONCLUSION: Female runners experienced a similar improvement in RE while wearing the VP when compared to previous studies, however this improvement dropped to 2.7% following a relatively short fatiguing run. Thus, improvements in RE from the VP shoes may not extend through the entire duration of some running events in certain athletes.

First-in-Human Study of the Biodistribution and Pharmacokinetics of 89Zr-CX-072, a Novel Immunopet Tracer Based on an Anti-PD-L1 Probody.

CX-072, a PD-L1-targeting Probody therapeutic, is engineered to be activated by tumor proteases that remove a masking peptide. To study effects on biodistribution and pharmacokinetics, we performed 89Zr-CX-072 positron emission tomography (PET) imaging. Patients received ∼1 mg, 37 MBq 89Zr-CX-072 plus 0, 4, or 9 mg unlabeled CX-072 and PET scans at days 2, 4, and 7. After that, treatment comprised 10 mg/kg CX-072 q2 weeks (n = 7) + 3 mg/kg ipilimumab q3w 4× (n = 1). Normal organ tracer uptake was expressed as standardized uptake value (SUV)mean and tumor uptake as SUVmax. PD-L1 expression was measured immunohistochemically in archival tumor tissue. Three of the eight patients included received 10-mg protein dose resulting in a blood pool mean SUVmean ± SD of 4.27 ± 0.45 on day 4, indicating sufficient available tracer. Tumor uptake was highest at day 7, with a geometric mean SUVmax 5.89 (n = 113) and present in all patients. The median follow-up was 12 weeks (4-76+). One patient experienced stable disease and two patients a partial response. PD-L1 tumor expression was 90% in one patient and ≤1% in the other patients. Mean SUVmean ± SD day 4 at 10 mg in the spleen was 8.56 ± 1.04, bone marrow 2.21 ± 0.46, and liver 4.97 ± 0.97. Four patients out of seven showed uptake in normal lymph nodes and Waldeyer's ring. The tracer was intact in the serum or plasma. 89Zr-CX-072 showed tumor uptake, even in lesions with ≤1% PD-L1 expression, and modest uptake in normal lymphoid organs, with no unexpected uptake in other healthy tissues.

Abstract 1395: Humanized GD2 antibody for targeted radiopharmaceutical therapy of human and canine osteosarcoma

Abstract Osteosarcoma (OS) is the most frequently diagnosed bone tumor in children in the United States. The prognosis for metastatic or recurrent OS has remained poor (5-year survival&amp;lt;30%) with no new effective therapies developed during the past 30 years. The high expression of tumor antigen, ganglioside GD2, on a variety of tumors, including OS, with its restricted expression on normal tissue makes GD2 an ideal target for anti-OS radiopharmaceutical therapy. Since human and canine OS shares many biological and molecular features and the prevalence of OS in dogs is 27 times higher than that in humans, spontaneously occurring OS in dogs has been shown to be an ideal model for testing new treatments for human translation. In this study, we evaluated a humanized GD2 antibody, hu3F8, that was developed for neuroblastoma therapy, as a potential delivery vector for targeted radiopharmaceutical therapy of human and canine OS.The cross immunoreactivity of hu3F8 with canine OS cells (OSCA78) and tissue, and human OS cells was confirmed by immunohistochemistry staining and flow cytometry. The binding affinity of hu3F8 to GD2 was assessed in vitro in OSCA78 and IMR32 (a human neuroblastoma cell line known expressing GD2) cell lines using 111In-DTPA-hu3F8. The dissociation constant Kd was 7.4 ± 1.0 nM for OSCA78, and 6.2 ± 1.9 nM for IMR32. Biodistribution study was performed in Nu/Nu mice bearing either OSCA78 tumor or IMR32 tumor. At 24 h after 111In-DTPA-hu3F8 injection, the highest uptake was observed in the tumor, followed by the blood, spleen, lung, and kidneys. The mean tumor uptake was 12.0% ID/g for OSCA78 tumors and 15.0% ID/g for IMR32 tumors, with a tumor-to-muscle ratio of 10.6 and 21.1, and a tumor-to-blood ratio of 1.1 and 2.4, for OSCA78 and IMR32 tumors, respectively. The 72 h biodistribution study revealed the highest uptake of 111In-DTPA-hu3F8 in both OSCA78 (28.0% ID/g) and IMR32 (51.6% ID/g ) tumors, with a tumor-to-muscle ratio of 93.3 and 206.6, and a tumor-to-blood ratio of 6.7 and 8.4, for OSCA78 tumors and IMR32 tumors, respectively. The improved uptake of 111In-DTPA-hu3F8 in tumors at 72 h was indicative of selective binding of 111In-DTPA-hu3F8 to GD2 expressing tumors. SPECT imaging showed that both OSCA78 and IMR32 tumors with 111In-DTPA-hu3F8 had superior contrast to the background, while 111In-DTPA-Rituximab (an irrelevant antibody) injected OSCA78-bearing mouse only showed moderate contrast to the background in the kidney.The cross immunoreactivity and high binding affinity of hu3F8 to canine OS cells/tissue and its ability to deliver an imaging payload (111In) suggest that conjugating hu3F8 with a radionuclide, such as alpha-emitter, 225Ac, may provide a potent radiopharmaceutical therapy for human and canine OS. Citation Format: Yingli Fu, Jing Yu, Ioanna Liatsou, Anders Josefsson, Yong Du, Jeffrey Bryan, Dara L. Kraitchman, George Sgouros. Humanized GD2 antibody for targeted radiopharmaceutical therapy of human and canine osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1395.

Determination of administered activities for the treatment of Graves' disease with iodine-131: Proposition of a simplified dosimetric procedure.

This prospective study included 35 patients suffering from Graves' disease (GD) clinically and biologically confirmed by endocrinologists, sent to the nuclear medicine department of CHU de Bab El Oued, Algiers for iodine-131 therapy. CHU de Bab El Oued is a tertiary hospital located in the center of the capital Algiers. The aim of this study is to propose a simplified dosimetric procedure which will initiate iodine-131 therapy of GD in particular and hyperthyroidism in general in Niger. The determination of the maximum uptake was performed with a Biodex external probe at 2 h, 4 h, and 24 h after the administration of 3 MBq of liquid iodine-131. The iodine-131 activities were determined using the Marinelli formula with a predefined effective half-life (Te) of 5 days and subsequently extrapolated half-life with kaleidagraph software. The statistical analysis was performed using an excel sheet and analyzed using the software package Statistica 10 (stat Soft, Tulsa, USA). the male:female gender ratio was1:4.5 and the mean age was 42.56 years (±7.14). The body mass index was within normal range with a value of 25.25 kg2(±0.42) and the mean average thyroid mass was equal to 24.05 (±10.53) g. The mean uptake value at 24 h was 43.24% (±17.68%) meanwhile the maximum uptake value was 46.28 (±21.13%). The estimated effective half-life (Te) was 5.44 days (±1.96) days which were different from the predefined Te of 5 days. The mean activity determined with fixed Te and 24 h uptake was 244.45 (±109.2) MBq and the mean activity calculated with both extrapolated Te and maximum uptake was 452.22 (±381.9) MBq. Empirical determination of activity in the treatment of GD gives higher activities (1.5 times) to patients than dosimetric methods based on the determination of extrapolated effective half-life.

Preclinical Evaluation of 89Zr-Df-IAB22M2C PET as an Imaging Biomarker for the Development of the GUCY2C-CD3 Bispecific PF-07062119 as a T Cell Engaging Therapy

PurposeA sensitive and specific imaging biomarker to monitor immune activation and quantify pharmacodynamic responses would be useful for development of immunomodulating anti-cancer agents. PF-07062119 is a T cell engaging bispecific antibody that binds to CD3 and guanylyl cyclase C, a protein that is over-expressed by colorectal cancers. Here, we used 89Zr-Df-IAB22M2C (89Zr-Df-Crefmirlimab), a human CD8-specific minibody to monitor CD8+ T cell infiltration into tumors by positron emission tomography. We investigated the ability of 89Zr-Df-IAB22M2C to track anti-tumor activity induced by PF-07062119 in a human CRC adoptive transfer mouse model (with injected activated/expanded human T cells), as well as the correlation of tumor radiotracer uptake with CD8+ immunohistochemical staining.ProceduresNOD SCID gamma mice bearing human CRC LS1034 tumors were treated with four different doses of PF-07062119, or a non-targeted CD3 BsAb control, and imaged with 89Zr-Df-IAB22M2C PET at days 4 and 9. Following PET/CT imaging, mice were euthanized and dissected for ex vivo distribution analysis of 89Zr-Df-IAB22M2C in tissues on days 4 and 9, with additional data collected on day 6 (supplementary). Data were analyzed and reported as standard uptake value and %ID/g for in vivo imaging and ex vivo tissue distribution. In addition, tumor tissues were evaluated by immunohistochemistry for CD8+ T cells.ResultsThe results demonstrated substantial mean uptake of 89Zr-Df-IAB22M2C (%ID/g) in PF-07062119-treated tumors, with significant increases in comparison to non-targeted BsAb-treated controls, as well as PF-07062119 dose-dependent responses over time of treatment. A moderate correlation was observed between tumor tissue radioactivity uptake and CD8+ cell density, demonstrating the value of the imaging agent for non-invasive assessment of intra-tumoral CD8+ T cells and the mechanism of action for PF-07062119.ConclusionImmune-imaging technologies for quantitative cellular measures would be a valuable biomarker in immunotherapeutic clinical development. We demonstrated a qualification of 89Zr-IAB22M2C PET to evaluate PD responses (mice) to a novel immunotherapeutic.

Tratamiento endoscópico del reflujo vesicoureteral primario en niños con dos materiales diferentes. Tasa de éxito alta y tasa de complicaciones baja: comparación entre Dexell y Vantris

Introduction and ObjectivesTo compare the results in terms of efficacy and safety of the endoscopic management for vesicoureteral reflux (VUR) in two different standardized primary VUR cohorts treated with Dexell and Vantris. Patients128 refluxing renal units (RRU) in 87 patients with primary VUR (64 females, 23 males). Patients with secondary VUR and severe bladder and bowel dysfunction were excluded. A total of 22 continent children with mild bladder-bowel dysfunction underwent bladder-bowel training before the implantation. All procedures were performed in the presence of sterile urine using a conventional subureteral transurethral injection technique. ResultsThere were no statistically significant differences between groups in terms of mean age, sex, RRU side, 99mTc-DMSA uptake, and reflux grade. The overall resolution rates based on the number of RRUs for up to three endoscopic treatments were 80% (56/70) in Dexell group and 94.8% (55/58) in Vantris group (p = 0.012). No postoperative recurrences or vesicoureteral junction obstructions were seen in any group. ConclusionsDexell and Vantris provided an effective and safe endoscopic VUR treatment in the early and mid-term follow up of children with primary VUR. The effectiveness of these substances, which can produce different mass effects with different particle sizes, in safe VUR resolution, needs further investigations.

Linking radiomic PET features with metabolic tissue parameters using a hybrid mathematical model of tumor growth

114 Objectives: The genetic diversity in tumor cells and the varying microenvironments lead to phenotypic heterogeneity within and between tumors (Marusyk et al., 2010), which can be assessed using PET imaging. More heterogeneous tumors may be more resilient to treatment and result in complications that are harder to treat (Hirata et al., 2017). Thus, understanding how tissue and tumor microparameters are linked to observable PET imaging features is of great interest, motivating the development of novel radiomics-based biomarkers. The objective of this work is to develop a multiscale mathematical model of tumor growth in vascularized tissue that can generate synthetic PET images of glucose metabolism. Using the model, we aim to establish a link between radiomic features and tissue microparameters. Methods: We simulate tumor growth using a hybrid mathematical model, which combines 1) grids of agents, namely autonomous decision-making entities representing blood vessels and different cell types (normal cells, tumor cells, hypoxic cells, necrotic cells), and 2) partial differential equation grids to simulate the tumor microenvironment (Robertson-Tessi, 2015). Blood is the source of oxygen and glucose (drugs or radionuclides can also be incorporated), which diffuse through tissue and are consumed by cells. In each simulation step, the state of each agent and the next action is determined based on the local microenvironment. The model uses realistic biological parameters, such as oxygen diffusion coefficient in tissue (1.62x10-5 cm2/s), consumption rates (2.5x10-18 to 2.0x10-15 mol/min/cell), and average cell size (20um). The oxygen consumption rate follows the Michaelis-Menten kinetics and is simplified to a constant for each cell type (Grimes et al, 2014). The simulated grid size was 1000x1000 cells (2x2 cm). The time-sequences of agent maps were converted to pseudo-standardized uptake value (pSUV) maps, assuming the relative glucose consumption rates 1, 8, 12, and 0 for normal, cancer, cancer hypoxic, and necrotic cells, respectively. pSUV maps were downsampled to a resolution of 3 mm (mid-point between pre-clinical and clinical PET resolution). The assumed PET tracer is a glucose analog, applicable to 18F-fluorodeoxyglucose (FDG). Results: To demonstrate the utility of our method, we used different combinations of microparameters to simulate 3 distinct tumor types (Fig. 1). Altered parameters included blood vessel density (types A,C: 20/mm2, B: 100/mm2), spatial arrangement (types A,C: random placement, B: uniform-density placement), and vascular network alteration by tumor cells such as vessel removal probability (types A,B: 1, C: 0.05). The resulting tumors of different types had very distinct phenotypes, which were visually distinguishable in the corresponding pSUV PET images (Fig. 2). The model produced diverse and realistic tumor growth rates, ranging from ~80 to ~310 days to reach a 1-cm tumor diameter (Fig. 3). Likewise, 4 radiomic features computed from the synthetic PET images of tumors (pSUV mean uptake, shape compactness, Haralick texture contrast and homogeneity), were significantly different between the tumor types. Specifically, the values for 1-cm tumors were: mean pSUV - 4.58 ± 0.03 (type A), 7.63 ± 0.72 (type B), 4.71 ± 0.04 (type C); Compactness - 0.91 ± 0.01 (A), 0.95 ± 0.01 (B), 0.94 ± 0.005 (C); Contrast - 1.67 ± 0.08 (A), 1.58 ± 0.04 (B), 1.36 ± 0.1 (C); Homogeneity - 0.71 ± 0.01 (A), 0.80 ± 0.006 (B), 0.79 ± 0.01 (C). From a combination of all 4 features, each tumor phenotype and set of tissue parameters can be uniquely identified. Conclusions: Realistic tumor growth can be achieved through modeling tissue and tumor microparameters. By changing the parameter values, distinctly different tumor phenotypes were obtained measurable through PET image radiomics. Hence, the model can help establish a link between tissue metabolic parameters and PET radiomics, and identify optimal radiomic features for tumor assessment.

Physiological responses and cycle characteristics during double-poling versus diagonal-stride roller-skiing in junior cross-country skiers

PurposeThis study aimed to compare physiological factors and cycle characteristics during cross-country (XC) roller-skiing at matched inclines and speeds using the double-poling (DP) and diagonal-stride (DS) sub-techniques in junior female and male XC skiers.MethodsTwenty-three well-trained junior XC skiers (11 women, 12 men; age 18.2 ± 1.2 yr.) completed two treadmill roller-skiing tests in a randomized order using either DP or DS. The exercise protocols were identical and included a 5 min warm-up, 4 × 5 min submaximal stages, and an incremental test to exhaustion, all performed at a 5° incline.ResultsNo significant three-way interactions were observed between sex, submaximal exercise intensity, and sub-technique. For the pooled sample, higher values were observed for DP versus DS during submaximal exercise for the mean oxygen uptake kinetics response time (33%), energy cost (18%), heart rate (HR) (9%), blood lactate concentration (5.1 versus 2.1 mmol·L−1), rating of perceived exertion (12%), and cycle rate (25%), while cycle length was lower (19%) (all P < 0.001). During the time-to-exhaustion (TTE) test, peak oxygen uptake (dot{V}O2peak), peak HR, and peak oxygen pulse were 8%, 2%, and 6% lower, respectively, for DP than DS, with a 29% shorter TTE during DP (pooled data, all P < 0.001).ConclusionIn well-trained junior XC skiers, DP was found to exert a greater physiological load than DS during uphill XC roller-skiing at submaximal intensities. During the TTE test, both female and male athletes were able to ski for longer and reached markedly higher dot{V}O2peak values when using DS compared to DP.

Assessment of normal reference values for thyroid uptake of technetium-99m pertechnetate in a Saudi population.

BACKGROUND: Thyrotoxicosis is a common medical problem. Thyroid nuclear imaging with either I123 or technetium-99m (Tc-99m) pertechnetate are used to determine the cause. Although I123 has been the standard technique, Tc-99m pertechnetate is now commonly used, acceptable and easier to perform. The commonly used normal value of Tc-99m pertechnetate is 1–4%, but lower normal values have been reported in different populations.OBJECTIVE: Determine normal reference range of Tc-99m pertechne-tate thyroid uptake for thyroid scintigraphy in Saudi Arabia.DESIGN: Retrospective, cross-sectional.SETTING: Nuclear medicine service at tertiary care center in Riyadh.PATIENTS AND METHODS: We used data from biochemically euthyroid patients who underwent a thyroid Tc-99m pertechnetate scan while having parathyroid scintigraphy for hyperparathyroidism between April 2009 to April 2019. Medical records and biochemical thyroid function tests were reviewed and Tc-99m pertechnetate thyroid uptake values were determined for each patient.MAIN OUTCOME MEASURES: Thyroid uptake of Tc-99m pertechne-tate in euthyroid patients.SAMPLE SIZE: 167RESULTS: The mean and median uptake of Tc-99m pertechnetate in euthyroid patients were 0.86% and 1.0%, respectively, and the inter-quartile range was 0.0–1.0%. The normal reference range in the study population was 0.2-2%. Thyroid uptake inversely correlated with age in females (r=−0.37, P<.001), males (r=−0.46, P=.001), and for all patients (r=?0.39, P<.0001).CONCLUSION: The range for normal thyroid Tc-99m pertechnetate was lower than the standard 1-4% range. Moreover, uptake decreased with age. Further studies are needed to establish the normal age-adjusted uptake for the thyroid Tc-99m pertechnetate scan.LIMITATIONS: Single center and retrospective.CONFLICT OF INTEREST: None.

Ontogenetic Shifts in Oxygen Uptake in Common Mudskipper (Periophthalmus kalolo) and its Role in Microhabitat Selection

Aims: The common mudskipper, Periophthalmus kalolo is a tropical, amphibious fish that utilizes both air and water as a respiratory medium. Adult oxygen uptake in water and air is well studied, but requirements of post-metamorphosed fish are virtually unknown. Our study quantifies how ontogenetic shifts across mudskipper life stage affects microhabitat choice.&#x0D; Study Design: metabolic rates in air and water were estimated for common mudskippers with mass values from 0.03 to 28.9 grams. Fish in each media were divided into 5 standard length classes (≤ 2.00, 2.01-4.00, 4.01-6.00, 6.01-8.00, ≥ 8.01 cm). Oxygen consumption for each class was calculated as the mean individual oxygen consumption for the group.&#x0D; Place and Duration of Study: Hoga Research Laboratory, Wakatobi National Park, Sulawesi, Indonesia, between June 14 and August 26, 2005.&#x0D; Methodology: Gilson manometry, and flow-through respirometery was used to determine respective aerial and aquatic oxygen uptake values for common mudskippers.&#x0D; Results: Mudskipper lengths varied by an order of magnitude (1.0 to 10.3 cm) and mass varied by three orders of magnitude (0.03 to 17.3 g). Mass-adjusted aerial metabolic rates of fish 2.00 cm or less in length, consumed up to ten times more oxygen than larger fish. whereas, aerial consumption values for size classes 2.01 cm and above did not differ significantly from each other (ANOVA: F4,112 = 40.29, P &lt; 0.0001; SNK, α = 0.05).&#x0D; Metabolic rates of submerged fish fell into two statistically distinct subsets. mudskippers with lengths of 4.00 cm or less had significantly higher metabolic rates than fish in remaining size classes; however, mean oxygen uptake values of fish within subsets did not differ significantly (ANOVA: F4,87 = 6.89, P &lt; 0.0001; SNK, α = 0.05). When oxygen consumption values at each size class were compared, only the smallest mudskipper size class (£ 2.00 cm) differed significantly between air and water (t-test: df = 34, t = 3.44, P &lt; 0.0001). Mudskippers 2 cm in standard length or smaller consumed over seven times more oxygen in air than water. All other size classes had similar rates of oxygen uptake in air and water and air:water oxygen uptake ratios fell to approximately 1:1.&#x0D; Conclusions: (1) Common mudskippers select different mangal habitats based on developmental life stage. (2) Small, post-metamorphosed fish &lt;2 mm in standard length, prefer cool shaded mangal areas, whereas, larger mudskippers utilize sun-exposed zones.&#x0D; (3) Post-metamorphosed fish, consume 10X more oxygen than all other size groups, confirming that juveniles are well suited to aerial respiration oxygen shortly after hatching. (4) Emerged post-metamorphosed fish exploit cooler, wetter pool habitats, thereby ameliorating problems of desiccation, excretion, and/or predation. (5) Ontogenetic shifts are a key life-history event in P. kalolo that promotes wider mangrove habitat use, and plays an important role in establishing common mudskipper as a key mangal species.

Quantitative dual isotope 123iodine/99mTc-MIBI scintigraphy: A new approach to rule out malignancy in thyroid nodules

BackgroundThe aim of this study was to evaluate the role of dual isotope 123Iodine/99mTc-MIBI thyroid scintigraphy (IMS) in discriminating between malignant and benign lesions in indeterminate nodules using quantitative analysis methods. MethodsThirty-five consecutive patients with thyroid nodules of indeterminate or non-diagnostic cytology and cold on 123Iodine scintigraphy (10 Bethesda I, 24 Bethesda III-IV, 1 in which cytology was impossible) underwent IMS between 2017 and 2019 with uptake quantification at two time points ahead of thyroidectomy: early and late. Images were analyzed by two blinded physicians. ResultsTwelve nodules were malignant and 23 benign on histopathology. Mean uptake values were lower in benign than in malignant nodules at both time points: early, 8.7±4.1 versus 12.9±3.5 (P=0.005); and late, 5.3±2.7 versus 7.7±1.1 (P=0.008). Interobserver reproducibility was excellent. The intraclass correlation coefficient was 0.86 in benign and 0.92 in malignant lesions for early uptake result (ER) and 0.94 and 0.85 respectively for late uptake result (LR). The optimal LR cut-off to exclude a diagnosis of malignancy was set at 5.9 . The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off were, respectively, 100%, 65.2%, 60%, 100% and 77.1%. ConclusionDespite some study limitations, quantitative analysis of 99mTc-MIBI thyroid scintigraphy had a good reproducibility, which could help to rule out malignancy in non-diagnostic or indeterminate thyroid nodules and thereby reducing the number of patients undergoing unnecessary surgery when LR is below 5.9.

Short-term exposure to elevated suspended sediment increases oxygen uptake of gilled larval Eastern Hellbender (Cryptobranchus alleganiensis) salamanders

Freshwater ecosystems are increasingly impacted by anthropogenic elevated levels of suspended sediment that may negatively affect aquatic organisms, including salamanders. Although increasing fine sediment in streams has been suggested as a reason for population declines, to date no study has empirically assessed the effect of suspended sediment on gilled larval Eastern Hellbenders (Cryptobranchus alleganiensis (Sonnini de Manoncourt and Latreille, 1801)), a critical life-history stage and a species of conservation concern. We used custom respirometers to elucidate effects of suspended sediments on larval Eastern Hellbender oxygen uptake in trials conducted in situ in Georgia (USA) streams. Mean oxygen uptake increased and was significantly higher in trials when larval salamanders were exposed to suspended sediment (mean = 5.06 mg O2/L for 800 mg/L of sediment treatment vs. 2.25 mg O2/L for 0.00 mg/L of sediment control). This may indicate elevated physiological stress in response to short-term exposure to suspended sediments. Qualitatively, individuals in both groups exhibited rocking behavior in response to low oxygen (hypoxia), albeit at different frequencies (sediment exposure = 7.6 rocks/min and control = 2.1 rocks/min). Larval salamanders may be able to temporarily compensate for low oxygen through increased rocking behavior when high suspended sediment loads are present, with future respirometry research needed.

Brain Resources: How Semantic Cueing Works in Mild Cognitive Impairment due to Alzheimer's Disease (MCI-AD).

Semantic cues in the Free and Cued Selective Reminding Test (FCRST) play a key role in the neuropsychological diagnosis of Amnesic Mild Cognitive Impairment due to Alzheimer’s Disease (MCI-AD); however, the neural bases of their impact of recall abilities are only partially understood. Here, we thus decided to investigate the relationships between brain metabolism and the FCSRT Index of Sensitivity of Cueing (ISC) in patients with MCI-AD and in healthy controls (HC). Materials: Thirty MCI-AD patients (age: 74.7 ± 5.7 years; education: 9.6 ± 4.6 years, MMSE score: 24.8 ± 3.3, 23 females) and seventeen HC (age: 66.5 ± 11.1 years; education: 11.53 ± 4.2 years, MMSE score: 28.4 ± 1.14, 10 females) who underwent neuropsychological evaluation and brain F-18 fluorodeoxyglucose Positron Emission Tomography (FDG-PET) were included in the study. Results: ISC was able to differentiate HC from MCI-AD subjects as shown by a ROC analysis (AUC of 0.978, effect size Hedges’s g = 2.89). MCI-AD subjects showed significant hypometabolism in posterior cortices, including bilateral inferior Parietal Lobule and Precuneus and Middle Temporal gyrus in the left hemisphere (VOI-1) compared to HC. ISC was positively correlated with brain metabolism in a single cluster (VOI-2) spanning the left prefrontal cortex (superior frontal gyrus) and anterior cingulate cortex (ACC) in the patient group (R2 = 0.526, p < 0.001), but not in HC. Mean uptake values of VOI-2 did not differ between HC and MCI-AD. The structural connectivity analysis showed that VOI-2 is connected with the temporal pole, the cingulate gyrus and the posterior temporal cortices in the left hemisphere. Conclusion: In MCI-AD, the relative preservation of frontal cortex metabolic levels and their correlation with the ISC suggest that the left frontal cortices play a significant role in maintaining a relatively good memory performance despite the presence of posterior hypometabolism in MCI-AD.

True ultra-low-dose amyloid PET/MRI enhanced with deep learning for clinical interpretation.

While sampled or short-frame realizations have shown the potential power of deep learning to reduce radiation dose for PET images, evidence in true injected ultra-low-dose cases is lacking. Therefore, we evaluated deep learning enhancement using a significantly reduced injected radiotracer protocol for amyloid PET/MRI. Eighteen participants underwent two separate 18F-florbetaben PET/MRI studies in which an ultra-low-dose (6.64 ± 3.57 MBq, 2.2 ± 1.3% of standard) or a standard-dose (300 ± 14 MBq) was injected. The PET counts from the standard-dose list-mode data were also undersampled to approximate an ultra-low-dose session. A pre-trained convolutional neural network was fine-tuned using MR images and either the injected or sampled ultra-low-dose PET as inputs. Image quality of the enhanced images was evaluated using three metrics (peak signal-to-noise ratio, structural similarity, and root mean square error), as well as the coefficient of variation (CV) for regional standard uptake value ratios (SUVRs). Mean cerebral uptake was correlated across image types to assess the validity of the sampled realizations. To judge clinical performance, four trained readers scored image quality on a five-point scale (using 15% non-inferiority limits for proportion of studies rated 3 or better) and classified cases into amyloid-positive and negative studies. The deep learning-enhanced PET images showed marked improvement on all quality metrics compared with the low-dose images as well as having generally similar regional CVs as the standard-dose. All enhanced images were non-inferior to their standard-dose counterparts. Accuracy for amyloid status was high (97.2% and 91.7% for images enhanced from injected and sampled ultra-low-dose data, respectively) which was similar to intra-reader reproducibility of standard-dose images (98.6%). Deep learning methods can synthesize diagnostic-quality PET images from ultra-low injected dose simultaneous PET/MRI data, demonstrating the general validity of sampled realizations and the potential to reduce dose significantly for amyloid imaging.

Characteristics of malignant thyroid lesions on [18F] fluorodeoxyglucose (FDG)-Positron emission tomography (PET)/Computed tomography (CT)

ObjectivesTo determine the imaging variables that can best differentiate malignant from benign thyroid lesions incidentally found on F-18 FDG PET/CT scans. MethodsAll F-18 FDG PET/CT studies starting from 2011 to end of 2016 were reviewed for incidental thyroid lesions or metabolic abnormalities. Only patients who were found to have FNAB or histopathology were included. Patients with known thyroid malignancy were excluded. Patients were analyzed for age, sex, SUVmax, non-enhanced CT tissue density in mean Hounsfield units (HU), uptake pattern (focal or diffuse) and gland morphology (MNG or diffuse). A control group of 15 patients with normal thyroid glands were used to assess the tissue density in HU for normal thyroid tissue. Sensitivity, specificity, PPV, NPV and accuracy to detect malignancy were calculated. Pearson Chi-square test was used to compare categorical variables while unpaired T-test and one way ANOVA test were used to compare means of continuous variables. ROC analysis was used to assess the best cut off points for SUVmax and HU. Regression analysis was used to detect the independent predictors for malignant lesions. ResultsBiopsy was unsatisfactory or indeterminate in 4/48 patients (8%). Only 44 patients (mean age 55.2 ± 14.7; 30 females (68 %)) with unequivocal FNAB or histopathology were included for further analysis. MNG was noted in 17/44 patients (38.6 %). Thyroid malignancy was found in 16/44 (36.4 %), benign thyroid lesions in 28/44 (63.6 %). Thyroid malignancies were 12 papillary, 1 follicular, 1 Hurthle cell neoplasm and 2 lymphoma. Benign lesions were 23 benign follicular or colloid nodules and 5 autoimmune thyroiditis. Focal FDG uptake pattern was more frequently associated with malignant lesions compared to benign lesions (75 % vs. 43 %; p = 0.039). The mean SUVmax and tissue density (HU) were both higher in malignant than benign lesions (8.8 ± 8.3 vs. 3.6 ± 1.9, p = 0.024) and (48.9 ± 12.7 vs. 32.9 ± 17.5, p = 0.003) respectively. The mean HU in the control group with normal thyroid tissue was 90 ± 7.4 significantly higher than in both the benign and malignant lesions (p < 0.001). ROC analysis revealed SUVmax cutoff of >4.7 and HU cutoff of >42 to best differentiate malignant from benign lesions. The sensitivity, specificity, PPV, NPV and accuracy to detect malignancy for SUVmax>4.7 were 68.8 %, 78.6 %, 64.8 %, 81.5 & 75.0 % (p = 0.002), for HU > 42 were 81.3.0 %, 75.0 %, 65.0 %, 87.5 & 77.3 % (p = 0.0003) and for both parameters combined were 87.5 %, 60.7 %, 56.0 %, 89.5 % and accuracy of 70.5 % (p = 0.002) respectively. Only HU > 42 and SUVmax>4.7 were independent predictors for malignancy with odd ratios 8.98 and 4.93 respectively. ConclusionA higher tissue density (HU > 42) and SUVmax>4.7 as well as tendency for focal uptake pattern are the most significant characteristics associated with malignant thyroid lesions occasionally detected on PET/CT.

Cardiac transthyretin amyloidosis 99mTc-DPD SPECT correlates with strain echocardiography and biomarkers

PurposeHereditary transthyretin-amyloid amyloidosis (ATTRv) is an underdiagnosed condition commonly manifesting as congestive heart failure. Recently, scintigraphy utilizing DPD as a tracer was shown to identify ATTRv and wild-type ATTR cardiomyopathy. The aim of this study was to determine the value of quantified scintigraphy utilizing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) single-photon emission computed tomography (SPECT)/CT, and to correlate its uptake with well-established cardiac functional parameters.MethodsForty-eight patients with genetically verified ATTRv type-A fibril composition, positive 99mTc-DPD SPECT/CT, were retrospectively analyzed. Manual mapping of volumes of interest (VOIs) on DPD SPECT/CT examinations was used to quantify heart uptake. DPD mean and maximum uptake together with a calculated DPD-based amyloid burden (DPDload) was correlated with echocardiographic strain values and cardiac biomarkers.ResultsStatistically significant correlations were seen in VOIs between DPD uptakes and the corresponding echocardiographic strain values. Furthermore, DPDload had a strong correlation with echocardiographic strain parameters and also correlated with biomarkers troponin T and logarithmic NT-ProBNP.ConclusionsIn patients with ATTRv cardiomyopathy, DPD SPECT/CT measures the amyloid distribution and provides information on cardiac amyloid load. DPD amyloid load correlates with functional cardiac parameters.

Acute Effects of Using Added Respiratory Dead Space Volume in a Cycling Sprint Interval Exercise Protocol: A Cross-Over Study.

Background: The aim of the study was to compare acute physiological, biochemical, and perceptual responses during sprint interval exercise (SIE) with breathing through a device increasing added respiratory dead space volume (ARDSV) and without the device. Methods: The study involved 11 healthy, physically active men (mean maximal oxygen uptake: 52.6 ± 8.2 mL∙kg1∙min−1). During four visits to a laboratory with a minimum interval of 72 h, they participated in (1) an incremental test on a cycle ergometer; (2) a familiarization session; (3) and (4) cross-over SIE sessions. SIE consisted of 6 × 10-s all-out bouts with 4-min active recovery. During one of the sessions the participants breathed through a 1200-mL ARDSv (SIEARDS). Results: The work performed was significantly higher by 4.4% during SIEARDS, with no differences in the fatigue index. The mean respiratory ventilation was significantly higher by 13.2%, and the mean oxygen uptake was higher by 31.3% during SIEARDS. Respiratory muscle strength did not change after the two SIE sessions. In SIEARDS, the mean pH turned out significantly lower (7.26 vs. 7.29), and the mean HCO3– concentration was higher by 7.6%. Average La− and rating of perceived exertion (RPE) did not differ between the sessions. Conclusions: Using ARDSV during SIE provokes respiratory acidosis, causes stronger acute physiological responses, and does not increase RPE.

Fiber density and cross‐section correlates with tau burden in entorhinal cortex in healthy older adults

AbstractBackgroundTau PET imaging, while highly predictive of the onset of dementia, requires injection of radioactive compound and costs much more than MRI scans. The goal of this study was to test whether multi‐shell diffusion MRI can generate diffusion measures that predict tau burden. While DTI measures such as fractional anisotropy (FA) and mean diffusivity have been examined in aging and dementia studies, the DTI model is now recognized as being too simplistic and has been shown to mistakenly calculated higher FA than controls in atrophied white matter. Multi‐shell diffusion MRI allows more accurate modeling of crossing fibers and has been demonstrated to detect atrophy in Alzheimer’s disease.MethodIn the current study, a sample of 14 healthy older adults was scanned with multi‐shell diffusion MRI and tau PET imaging using [18F]MK‐6240 tracer. For 10 of the participants, diffusion was obtained on average 222 days before tau PET while the 4 other participants were scanned with diffusion MRI 211 days after tau PET. Standardized uptake value ratio (SUVR) for the left and the right entorhinal cortex were quantified relative to the cerebellar mean uptake. Diffusion data were processed through MRtrix’s fiber‐based analysis pipeline to obtain the whole brain fiber density and cross‐section (FDC) measure. Using tracts connected to the parahippocampal gyrus as masks, we tested whether FDC of the fibers in the white matter tracts connected to the parahippocampal gyrus correlated negatively with the tau SUVR in the entorhinal cortex within each hemisphere, correcting for age.ResultAfter correction for multiple comparisons using family‐wise error approach, FDC for fibers connected to the left parahippocampal gyrus were negatively correlated with the left entorhinal tau SUVR as shown in figure attached. The mean FDC over the significant fibers and EC tau SUVR showed that r = ‐.707, p=0.007.ConclusionThe negative correlation supports our hypothesis that greater tau burden is associated with lower fiber density and cross‐section in white matter tracts directly connected to the parahippocampal cortex. This encouraging result demonstrates the potential for multi‐shell diffusion as an alternative to PET for early detection of tau burden in cognitively healthy older adults.