Relative Perfusion Research Articles

Role of Qualitative and Quantitative Indocyanine Green Angiography to Assess Mastectomy Skin Flaps Perfusion: A Prospective Monocentric Experience.

Mastectomy skin flap (MSF) necrosis remains a significant complication in breast reconstruction. This study aims to identify a correlation between the qualitative and quantitative analysis of the MSF perfusion grade and the skin necrosis rate 1 month after surgery using indocyanine green angiography (ICGA), focusing on lag time and perfusion metrics. Consecutive women scheduled for nipple/skin-sparing/skin-reducing mastectomy between May 2020 and October 2022 were prospectively enrolled. Patients were divided into Group 1 in the absence of superficial and full-thickness necrosis (SN; FTN) and Group 2 in the presence of both. Demographic data, lag time T1 (time between ICG injection and the initial perfusion of the least perfused MSF area), ICG-Q1, and ICG-Q% (absolute and relative perfusion values of the least vascularized area) were collected. 76 breasts were considered. FTN was reported in 8 breasts (10.5%) and SN in 4 (5.2%). The 2 groups statistically differ in T1 (Group2 > Group1), ICG-Q1, and ICG-Q% (Group1 > Group2) (P < 0.05). T1 longer than 170 seconds, body mass index, previous chemo/radiotherapy, arterial hypertension, breast weight, type of surgery, and ICG quantitative values can help in predicting MSF necrosis. MSF qualitative and quantitative perfusion evaluation can be helpful to prevent MSF necrosis. However, it should be considered together with the patient's characteristics, the type of surgery, and T1. In this way, it is possible to predict the risk of MSF necrosis and plan the best reconstructive strategy.

How Good Are We Really? Underestimating the Extent of Obstructive CAD With SPECT and PET Relative Myocardial Perfusion Imaging and With PET Absolute Myocardial Blood Flow Measurement

How Good Are We Really? Underestimating the Extent of Obstructive CAD With SPECT and PET Relative Myocardial Perfusion Imaging and With PET Absolute Myocardial Blood Flow Measurement

Parametric imaging of myocardial blood flow with 82Rb PET: An accuracy and image quality analysis

BackgroundWe aimed to develop a framework for generating three-dimensional (3D) myocardial blood flow (MBF) images, computing their accuracy against clinically validated two-dimensional (2D) polar MBF maps of the left ventricle, and evaluating their improvements in image quality over relative myocardial perfusion imaging (MPI). MethodsN = 40 patients with a wide range of defect severities and uptake dynamics were retrospectively studied. The FlowQuant™ software was used to generate reference MPI and polar MBF maps and was adapted for voxel-wise MBF mapping. We evaluated agreement between parametric vs polar values for MBF at rest and stress and for reserve (stress/rest MBF). We also assessed improvements in image quality, assessed by signal-to-noise ratio, contrast-to-noise ratio, tissue-to-blood ratio, and defect severity, from relative MPI to MBF. ResultsThere was excellent agreement between 3D parametric and 2D polar maps for all flow parameters (interclass correlation coefficient >0.96), albeit with minimal bias (<8%) for rest and stress MBF at the patient level. Image quality substantially improved from MPI to MBF in every patient for all image-quality metrics (P < 0.0001) ConclusionsWe developed a robust methodology for producing highly accurate 3D MBF images exhibiting considerably improved image quality compared to relative MPI commonly used in clinical practice.

Breast Modular Resection (BMR) in Nipple-Sparing Mastectomy (NSM) With Intraoperative Laser Speckle Contrast Imaging (LSCI) Monitoring Improved Surgical Training Outcome Among Fellows

BackgroundNipple-sparing mastectomy (NSM) and skin-sparing mastectomy (SSM) are challenging for surgical training among fellow trainees. We developed a surgical training course with novel concept of breast modular resection (BMR) for NSM/SSM procedure, and performed this study to investigate whether BMR could improve surgical outcomes compared to classical procedure resection (CPR). MethodsThe records of 105 breast cancer patients undergoing NSM/SSM with immediate reconstruction performed by fellow trainees were reviewed. Clinicopathological characteristics and surgical outcomes were compared between 2 groups. Laser speckle contrast imaging (LSCI) was performed to intraoperatively evaluate the blood supply of the NAC, and the absolute perfusion unit (PU) values and relative perfusion unit (rPU) values were further compared. ResultsSurgical training outcomes of BMR group (N = 52) were insignificantly improved compared to CPR group (N = 53). The rates of NAC necrosis, flap necrosis and implant removal all reduced respectively. Among the 60 NSM patients, the blood loss (P = .011) and surgery time (P < .001) was significantly reduced in BMR group (N = 30) and all the other outcomes were insignificantly improved. Both the absolute PU values and rPU values were significantly higher among patients without NAC necrosis (P < .001). The absolute PU values were significantly higher in BMR group (P = .002). ConclusionCompared to CPR, the BMR-based surgical training course for NSM demonstrated the reduction in complications and operating time, offering a potential streamlined, efficient, and safe method for NSM procedure. LSCI was effective for intraoperative visualized evaluation of NAC blood supply and could provide effective real-time feedback for fellow trainees.

Dye-less quantification of tissue perfusion by laser speckle contrast imaging is equivalent to quantified indocyanine green in a porcine model.

Subjective surgeon interpretation of near-infrared perfusion video is limited by low inter-observer agreement and poor correlation to clinical outcomes. In contrast, quantification of indocyanine green fluorescence video (Q-ICG) correlates with histologic level of perfusion as well as clinical outcomes. Measuring dye volume over time, however, has limitations, such as it is not on-demand, has poor spatial resolution, and is not easily repeatable. Laser speckle contrast imaging quantification (Q-LSCI) is a real-time, dye-free alternative, but further validation is needed. We hypothesize that Q-LSCI will distinguish ischemic tissue and correlate over a range of perfusion levels equivalent to Q-ICG. Nine sections of intestine in three swine were devascularized. Pairs of indocyanine green fluorescence imaging and laser speckle contrast imaging video were quantified within perfused, watershed, and ischemic regions. Q-ICG used normalized peak inflow slope. Q-LSCI methods were laser speckle perfusion units (LSPU), the base unit of laser speckle imaging, relative perfusion units (RPU), a previously described methodology which utilizes an internal control, and zero-lag normalized cross-correlation (X-Corr), to investigate if the signal deviations convey accurate perfusion information. We determine the ability to distinguish ischemic regions and correlation to Q-ICG over a perfusion gradient. All modalities distinguished ischemic from perfused regions of interest; Q-ICG values of 0.028 and 0.155 (p < 0.001); RPU values of 0.15 and 0.68 (p < 0.001); and X-corr values of 0.73 and 0.24 (p < 0.001). Over a range of perfusion levels, RPU had the best correlation with Q-ICG (r = 0.79, p < 0.001) compared with LSPU (r = 0.74, p < 0.001) and X-Corr (r = 0.46, p < 0.001). These results demonstrate that Q-LSCI discriminates ischemic from perfused tissue and represents similar perfusion information over a broad range of perfusion levels comparable to clinically validated Q-ICG. This suggests that Q-LSCI might offer clinically predictive real-time dye-free quantification of tissue perfusion. Further work should include validation in histologic studies and human clinical trials.

Cerebral perfusion metrics calculated directly from a hypoxia-induced step change in deoxyhemoglobin

Resting cerebral perfusion metrics can be calculated from the MRI ΔR2* signal during the first passage of an intravascular bolus of a Gadolinium-based contrast agent (GBCA), or more recently, a transient hypoxia-induced change in the concentration of deoxyhemoglobin ([dOHb]). Conventional analysis follows a proxy process that includes deconvolution of an arterial input function (AIF) in a tracer kinetic model. We hypothesized that the step reduction in magnetic susceptibility accompanying a step decrease in [dOHb] that occurs when a single breath of oxygen terminates a brief episode of lung hypoxia permits direct calculation of relative perfusion metrics. The time course of the ΔR2* signal response enables both the discrimination of blood arrival times and the time course of voxel filling. We calculated the perfusion metrics implied by this step signal change in seven healthy volunteers and compared them to those from conventional analyses of GBCA and dOHb using their AIF and indicator dilution theory. Voxel-wise maps of relative cerebral blood flow and relative cerebral blood volume had a high spatial and magnitude congruence for all three analyses (r > 0.9) and were similar in appearance to published maps. The mean (SD) transit times (s) in grey and white matter respectively for the step response (7.4 (1.1), 8.05 (1.71)) were greater than those for GBCA (2.6 (0.45), 3.54 (0.83)) attributable to the nature of their respective calculation models. In conclusion we believe these calculations of perfusion metrics derived directly from ΔR2* have superior merit to calculations via AIF by virtue of being calculated from a direct signal rather than through a proxy model which encompasses errors inherent in designating an AIF and performing deconvolution calculations.

Dual-wavelength dye laser combined with betamethasone injection for treatment of keloids: protocol of a randomised controlled trial

IntroductionKeloids, benign fibroproliferative tumours characterised by excessive fibroblast proliferation and over-deposition of extracellular matrix, pose a therapeutic challenge with high recurrence rates. Betamethasone (diprospan) injection (BI) is one of the...

[15O]H2O myocardial perfusion positron emission tomography: Added value of relative stress perfusion deficit in the prediction of significant coronary artery stenosis in a mixedpopulation

BackgroundIt remains unknown whether estimation of the relative stress perfusion deficit offers added value in the prediction of significant coronary artery stenosis in myocardial perfusion imaging with [15O]H2O positron emission tomography (PET) in a population with high prevalence of established cardiac disease. MethodsDuring eight months, we consecutively included all patients undergoing [15O]H2O PET and subsequent invasive coronary angiography (ICA). Significant stenosis was defined from ICA as fractional flow reserve ≤.8 or coronary artery narrowing of ≥70%. We calculated absolute and relative total perfusion deficits (aTPD and rTPD, respectively) as semiquantitative measures of the extent and severity of reduced stress perfusion. A multivariate logistic regression analysis was performed to test the adjusted associations (odds ratio (OR) with 95% CI) with significant coronary artery stenosis. ResultsOf 800 patients undergoing [15O]H2O PET, 144 underwent ICA, where 142 patients had aTPD of ≥3% and 79 (55%) of these had at least one significant stenosis. In an adjusted analysis, rTPD (OR10% increase = 2.12 (1.44-3.12), P < .001), previous coronary artery bypass grafting (CABG) (OR = .11 (.03-.36), P < .001) and reduced left ventricular ejection fraction (LVEF) (OR = .25 (.08-.84), P = .02) were independently associated with significant stenosis, whereas the association with aTPD (OR10% increase = 1.14 (.98-1.32), P = .08) was modest. ConclusionsIn the presence of an absolute perfusion deficit (aTPD of ≥3%), rTPD may improve the prediction of significant stenosis in a heterogeneous population of patients examined with [15O]H2O PET. Furthermore, previous CABG and reduced LVEF are associated with nonstenotic perfusion deficiencies, suggesting caution when interpreting myocardial perfusion imaging in such patients.

Role of local vasoconstrictors in diving performance of two pinniped species

Diving mammals extend submergence time through bradycardia and reduced peripheral perfusion to certain tissues. Thus, local blood flow regulation under hypoxia may be an essential physiological strategy that fine-tunes metabolic expenditures during breath-hold. We focused on a potent local vasoconstrictor, Endothelin-1 (ET1) and its receptors ETR-A and ETR-B, to determine their potential role in mammalian diving. We hypothesized that less perfused organs (kidney) would have higher signatures of local vasoconstriction (i.e. higher ET1 and receptors), compared to organs known to have higher relative perfusion underwater (heart/left ventricle). Additionally, we compared pinniped species with higher (Weddell seal) and lower (California sea lion) relative dive capabilities. Differences in mRNA expression of vasoconstrictive elements were assessed by 2-way ANOVA to compare tissue and species. In adult animals (n=7 both species) there were significant differences in expression of ET1 between species (F1,16=9.2, p=0.08) and tissues (F1,16=18.4, p=0.0006), with sea lions having consistently higher levels of ET1. ET1 expression was highest in the kidney, with sea lion kidney expressing 25x more ET1 mRNA than heart (posthoc p=0.0007). The expression ratio of ET A and B receptors also differed across tissue (F1,16=19.83 p=0.0004) with B/A highest in the kidney in both species. This is counter to expectations that submergence capability would relate to vasoconstriction potential across species, but supports the hypothesis that within a species, the less-perfused kidney should demonstrate higher potential for local vasoconstriction compared to the heart. Relative expression of ET receptors between tissues also runs counter to our hypothesis. In both divers, the heart expresses relatively more ETR-A, which has a critical role in vasoconstrictive signaling. On the other hand, ETR-B can signal for either vasoconstriction or vasodilation depending on its location within the endothelium or smooth muscle. Kidney in both species expresses relatively more ETR-B, indicating potential for nuanced vasoregulatory control through the endothelin pathway in this tissue. Receptor localization will be determined by immuno-staining to investigate functional differences between tissues. We also investigated the development of diving by comparing the same biomarkers in adults versus pups (n=10 seals, n=3 sea lions) using a separate 2-way ANOVA for each species. We expected that signatures of vasoregulatory potential would be less evident in the novice diving pups. Concordantly, ET1 is lower in sea lion pups than adults (F1,12=5.097, p=0.043); ET1 mRNA is 23x lower in the pup kidney compared to adult (posthoc p=0.02). Receptor expression followed the same patterns in both species, with the highest expression of ETR-A noted in the pup heart, indicating high vasoconstrictive potential in pups, but through tissue specific mechanisms. These results point to differences in the control of local vasoconstriction that occur with development and highlight the physiological components essential to the development of diving. Funding by NSF #2020706. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 1100: Soluble Guanylate Cyclase Activators As Potential Novel Pad Therapeutics

Introduction: Peripheral arterial disease (PAD) is major cause of limb loss in the United States with limited treatment modalities. Understanding the genetic etiology of PAD may provide rationale for novel therapeutic strategies. Here, we report a novel association between PAD and a likely endothelial cell specific cis-regulatory element of Nitric Oxide Synthase 3 ( NOS3 ). We hypothesize that targeting of the nitric oxide (NO)-cyclic GMP (cGMP) axis with Riociguat, an FDA-approved soluble guanylate cyclase (sGC) activator, will improve perfusion and exercise capacity in a murine PAD model. Methods: We meta-analyzed genetic associations with PAD using summary statistics from European participants in the UK Biobank (UKB), Copenhagen Hospital Biobank - Cardiovascular Disease Cohort and Danish Blood Donor Study (CHB-CVDC/DBDS), and the Million Veteran Program (MVP). Human NOS3 deficiency was modeled using Enos +/- mice with C57/B6 controls. We induced hindlimb ischemia (HLI) via double ligation of the femoral artery as described previously. Riociguat (3mg/kg/day) was administered 4 days prior and 28 days after HLI induction. We measured exercise capacity by placing animals on a treadmill with increasing speed and incline. We measured hindlimb perfusion using laser doppler perfusion imaging and assessed relative perfusion of the ischemic limb to the contralateral control limb. Results: We identified novel association of the minor allele of rs3918226, which lies within the promoter of NOS3, with PAD (OR: 1.06; 95% CI: 1.04-1.09; P = 1.3 x 10-9). Induction of hindlimb ischemia in Enos +/- animals resulted in impaired exercise capacity compared to wild-type controls. In Riociguat-treated Enos +/- mice, we observed a significant increase in distance traveled during exercise testing at 14 days which was sustained for the duration of the study period (276 vs 156 meters, p&lt;0.05). We did not find a significant improvement in hindlimb perfusion over the course of the study period. Conclusion: Here, we identify a novel genetic association with PAD and demonstrate that in a genetic model of PAD we can improve exercise capacity by targeting the NO-cGMP axis with Riociguat. Future studies will assess the clinical utility of sGC activators like Riociguat in humans.

Effects of positive end-expiratory pressure on pulmonary perfusion distribution and intrapulmonary shunt during one-lung ventilation in pigs A randomized crossover study.

During one-lung ventilation (OLV), positive end-expiratory pressure (PEEP) can improve lung aeration, but might over-distend lung units and increase intrapulmonary shunt. We hypothesized that higher PEEP shifts pulmonary perfusion from the ventilated to the non-ventilated lung, resulting in a U-shaped relationship with intrapulmonary shunt during OLV. In nine anesthetized female pigs, a thoracotomy was performed and intravenous lipopolysaccharide infused to mimic the inflammatory response of thoracic surgery. Animals underwent OLV in supine position with PEEP of 0 cmH2O, 5 cmH2O, titrated to best respiratory system compliance, and 15 cmH2O (PEEP0, PEEP5, PEEPtitr, and PEEP15, respectively, 45 min each, Latin square sequence). Respiratory, hemodynamic, and gas exchange variables were measured. The distributions of perfusion and ventilation were determined by i.v. fluorescent microspheres and computed tomography, respectively. Compared to two lung ventilation, the driving pressure increased with OLV, irrespective of the PEEP level. During OLV, cardiac output was lower at PEEP15 (5.5 ± 1.5 l/min) than PEEP0 (7.6 ± 3 l/min) and PEEP5 (7.4 ± 2.9 l/min; P=0.004), while the intrapulmonary shunt was highest at PEEP0 (PEEP0: 48.1 ± 14.4 %; PEEP5: 42.4 ± 14.8 %; PEEPtitr: 37.8 ± 11.0 %; PEEP15: 39.0 ± 10.7 %; P=0.027). The relative perfusion of the ventilated lung did not differ among PEEP levels (PEEP0: 65.0 ± 10.6 %; PEEP5:68.7 ± 8.7 %; PEEPtitr: 68.2 ± 10.5 %; PEEP15: 58.4 ± 12.8%; P=0.096), but the centers of relative perfusion and ventilation in the ventilated lung shifted from ventral to dorsal, and from cranial to caudal zones with increasing PEEP. In this experimental model of thoracic surgery, higher PEEP during OLV did not shift the perfusion from the ventilated to the non-ventilated lung, thus not increasing intrapulmonary shunt. This study was registered and approved by the Landesdirektion Dresden, Germany (25-5131/496/33).

Myocardial blood flow quantification with SPECT

IntroductionThe addition of absolute myocardial blood flow (MBF) data improves the diagnostic and prognostic accuracy of relative perfusion imaging with nuclear medicine. Cardiac-specific gamma cameras allow measurement of MBF with SPECT. MethodsThis paper reviews the evidence supporting the use of SPECT to measure myocardial blood flow (MBF). Studies have evaluated SPECT MBF in large animal models and compared it in humans with invasive angiographic measurements and against the clinical standard of PET MBF. The repeatability of SPECT MBF has been determined in both single-site and multi-center trials. ResultsSPECT MBF has excellent correlation with microspheres in an animal model, with the number of stenoses and fractional flow reserve, and with PET-derived MBF. The inter-user coefficient of variability is ∼20% while the COV of test-retest MBF is ∼30%. SPECT MBF improves the sensitivity and specificity of the detection of multi-vessel disease over relative perfusion imaging and provides incremental value in predicting adverse cardiac events. ConclusionSPECT MBF is a promising technique for providing clinically valuable information in the assessment of coronary artery disease.

Prevalence of balanced ischemia on positron emission tomography relative perfusion imaging among patients with high-risk coronary artery disease

Prevalence of balanced ischemia on positron emission tomography relative perfusion imaging among patients with high-risk coronary artery disease

Optimization of lung ventilation and perfusion in anesthetized horses using a ventilation mode with flow-limited expiration.

To investigate the mechanisms underlying the improved arterial oxygenation described with flow-limited expiration (FLEX) ventilation in anesthetized horses. 5 healthy adult research horses. Horses underwent volume-controlled ventilation for 60 minutes (VCV1), followed by 60 minutes of FLEX, and 30 minutes of VCV (VCV2). Main outcomes included the arterial partial pressure of oxygen-to-Fio2 (PF) ratio and electrical impedance tomography (EIT)-derived functional indices at the end of each phase. The EIT data were used to create regional maps of relative lung ventilation and perfusion as well as regional maps of ventilation/perfusion (V/Q) ratios. Ventilation indices derived from EIT included the fraction of expired volume in 1 second (FEV1; %) and the time it took for the EIT signal to drop to 50% of the peak signal at end-inspiration (TClose50; seconds). Data were analyzed with 2-way ANOVA for repeated measures. P < .05 was considered significant. The PF ratio increased significantly with FLEX compared to both VCV1 and VCV2 (P < .01). There were no differences in the relative distribution of ventilation nor perfusion between ventilation strategies. However, when ventilation and perfusion were superimposed and V/Q ratio maps were constructed, FLEX had a homogenizing effect toward values of 1.0. The FEV1 was shorter (P < .01) and the TClose50 was longer (P < .001) in all regions during FLEX compared to both VCV1 and VCV2. Our findings suggest that FLEX ventilation in anesthetized horses enhances regional V/Q matching, likely by prolonging expiratory aeration and reducing airway closure.

The diagnostic efficiency of integration of 2HG MRS and IVIM versus individual parameters for predicting IDH mutation status in gliomas in clinical scenarios: A retrospective study.

Currently, there remains a scarcity of established preoperative tests to accurately predict the isocitrate dehydrogenase (IDH) mutation status in clinical scenarios, with limited research has explored the potential synergistic diagnostic performance among metabolite, perfusion, and diffusion parameters. To address this issue, we aimed to develop an imaging protocol that integrated 2-hydroxyglutarate (2HG) magnetic resonance spectroscopy (MRS) and intravoxel incoherent motion (IVIM) by comprehensively assessing metabolic, cellular, and angiogenic changes caused by IDH mutations, and explored the diagnostic efficiency of this imaging protocol for predicting IDH mutation status in clinical scenarios. Patients who met the inclusion criteria were categorized into two groups: IDH-wild type (IDH-WT) group and IDH-mutant (IDH-MT) group. Subsequently, we quantified the 2HG concentration, the relative apparent diffusion coefficient (rADC), the relative true diffusion coefficient value (rD), the relative pseudo-diffusion coefficient (rD*) and the relative perfusion fraction value (rf). Intergroup differences were estimated using t-test and Mann-Whitney U test. Finally, we performed receiver operating characteristic (ROC) curve and DeLong's test to evaluate and compare the diagnostic performance of individual parameters and their combinations. 64 patients (female, 21; male, 43; age, 47.0 ± 13.7years) were enrolled. Compared with IDH-WT gliomas, IDH-MT gliomas had higher 2HG concentration, rADC and rD (P < 0.001), and lower rD* (P = 0.013). The ROC curve demonstrated that 2HG + rD + rD* exhibited the highest areas under curve (AUC) value (0.967, 95%CI 0.889-0.996) for discriminating IDH mutation status. Compared with each individual parameter, the predictive efficiency of 2HG + rADC + rD* and 2HG + rD + rD* shows a statistically significant enhancement (DeLong's test: P < 0.05). The integration of 2HG MRS and IVIM significantly improves the diagnostic efficiency for predicting IDH mutation status in clinical scenarios.

99mTc-HMPAO SPECT Perfusion Signatures Associated With Clinical Progression in Patients With Isolated REM Sleep Behavior Disorder.

Idiopathic/isolated REM sleep behavior disorder (iRBD) is associated with dementia with Lewy bodies and Parkinson disease. Despite evidence of abnormal cerebral perfusion in iRBD, there is currently no pattern that can predict whether an individual will develop dementia with Lewy bodies or Parkinson disease. The objective was to identify a perfusion signature associated with conversion to dementia with Lewy bodies in iRBD. Patients with iRBD underwent video-polysomnography, neurologic and neuropsychological assessments, and baseline 99mTc-HMPAO SPECT to assess relative cerebral blood flow. Partial least squares correlation was used to identify latent variables that maximized covariance between 27 clinical features and relative gray matter perfusion. Patient-specific scores on the latent variables were used to test the association with conversion to dementia with Lewy bodies compared with that with Parkinson disease. The signature's expression was also assessed in 24 patients with iRBD who underwent a second perfusion scan, 22 healthy controls, and 19 individuals with Parkinson disease. Of the 137 participants, 93 underwent SPECT processing, namely 52 patients with iRBD (67.9 years, 73% men), 19 patients with Parkinson disease (67.3 years, 37% men), and 22 controls (67.0 years, 73% men). Of the 47 patients with iRBD followed up longitudinally (4.5 years), 12 (26%) developed a manifest synucleinopathy (4 dementia with Lewy bodies and 8 Parkinson disease). Analysis revealed 2 latent variables between relative blood flow and clinical features: the first was associated with a broad set of features that included motor, cognitive, and perceptual variables, age, and sex; the second was mostly associated with cognitive features and RBD duration. When brought back into the patient's space, the expression of the first variable was associated with conversion to a manifest synucleinopathy, whereas the second was associated with conversion to dementia with Lewy bodies. The expression of the patterns changed over time and was associated with worse motor features. This study identified a brain perfusion signature associated with cognitive impairment in iRBD and transition to dementia with Lewy bodies. This signature, which can be derived from individual scans, has the potential to be developed into a biomarker that predicts dementia with Lewy bodies in at-risk individuals.

Synaptic loss and its association with symptom severity in Parkinson’s disease

Parkinson’s disease (PD) is the fastest growing neurodegenerative disease, but at present there is no cure, nor any disease-modifying treatments. Synaptic biomarkers from in vivo imaging have shown promise in imaging loss of synapses in PD and other neurodegenerative disorders. Here, we provide new clinical insights from a cross-sectional, high-resolution positron emission tomography (PET) study of 30 PD individuals and 30 age- and sex-matched healthy controls (HC) with the radiotracer [11C]UCB-J, which binds to synaptic vesicle glycoprotein 2A (SV2A), and is therefore, a biomarker of synaptic density in the living brain. We also examined a measure of relative brain perfusion from the early part of the same PET scan. Our results provide evidence for synaptic density loss in the substantia nigra that had been previously reported, but also extend this to other early-Braak stage regions known to be affected in PD (brainstem, caudate, olfactory cortex). Importantly, we also found a direct association between synaptic density loss in the nigra and severity of symptoms in patients. A greater extent and wider distribution of synaptic density loss in PD patients with longer illness duration suggests that [11C]UCB-J PET can be used to measure synapse loss with disease progression. We also demonstrate lower brain perfusion in PD vs. HC groups, with a greater extent of abnormalities in those with longer duration of illness, suggesting that [11C]UCB-J PET can simultaneously provide information on changes in brain perfusion. These results implicate synaptic imaging as a useful PD biomarker for future disease-modifying interventions.

Characterization of placentome vascular perfusion in relation to pregnancy associated glycoproteins throughout gestation in pregnant beef heifers

During pregnancy, blood flow to the uterus changes to support fetal demand. Placentomes serve as vascular attachment sites on the placenta for exchange of gases, nutrients, and metabolic products. Non-invasive methods of ultrasonography and biomarkers have been described to assess placental health and fetal viability. Pregnancy associated glycoproteins (PAGs) are produced by the ruminant placenta and are detected in maternal circulation. In cattle, changes in circulating PAG concentrations are associated with embryonic and fetal outcomes. The objective of this study was to determine the association between placentome blood perfusion and circulating PAG concentrations as they relate to the health of the developing fetus. We hypothesized that placentome perfusion and PAG concentration will be positively correlated and associated with neonatal outcome. A prospective, observational study was designed using 26 pregnant, nulliparous, Angus heifers in which PAG concentration and placentome blood perfusion were assessed throughout gestation, with assessment of calving characteristics following parturition. Placentome blood perfusion was visualized at 30-day intervals via transrectal Doppler ultrasonography with power flow function. Ultrasound images were analyzed using ImageJ software to determine the percent area of perfusion and integrated pixel densities. Venous blood was collected and PAG concentrations were determined via serum PAG enzyme-linked immunoassay. Mean placentome blood perfusion increased as gestation advanced. PAG concentrations demonstrated the expected temporal trend, increasing with gestation length, and were positively linearly correlated with placentome perfusion (P < 0.0001). The relationship identified between circulating PAG concentration and placentome blood perfusion suggests the use of transrectal power flow Doppler ultrasonography as a noninvasive technique to determine placental blood flow morphometrics to assess conceptus wellbeing throughout pregnancy.

Kinetic analysis of cardiac dynamic 18F-Florbetapir PET in healthy volunteers and amyloidosis patients: A pilot study

ObjectivesThis study aimed to explore the potential of full dynamic PET kinetic analysis in assessing amyloid binding and perfusion in the cardiac region using 18F-Florbetapir PET, establishing a quantitative approach in the clinical assessment of cardiac amyloidosis disease. Materials & methodsThe distribution volume ratios (DVRs) and the relative transport rate constant (R1), were estimated by a pseudo-simplified reference tissue model (pSRTM2) and pseudo-Logan plot (pLogan plot) with kidney reference for the region of interest-based and voxel-wise-based analyses. The parametric images generated using the pSRTM2 and linear regression with spatially constrained (LRSC) algorithm were then evaluated. Semi-quantitative analyses include standardized uptake value ratios at the early phase (SUVREP, 0.5–5 min) and late phase (SUVRLP, 50–60 min) were also calculated. ResultsTen participants [7 healthy controls (HC) and 3 cardiac amyloidosis (CA) subjects] underwent a 60-min dynamic 18F-Florbetapir PET scan. The DVRs estimated from pSRTM2 and Logan plot were significantly increased (HC vs CA; DVRpSRTM2: 0.95 ± 0.11 vs 2.77 ± 0.42, t’(2.13) = 7.39, P = 0.015; DVRLogan: 0.80 ± 0.12 vs 2.90 ± 0.55, t’(2.08) = 6.56, P = 0.020), and R1 were remarkably decreased in CA groups, as compared to HCs (HC vs CA; 1.08 ± 0.37 vs 0.56 ± 0.10, t’(7.63) = 3.38, P = 0.010). The SUVREP and SUVRLP were highly correlated to R1 (r = 0.97, P < 0.001) and DVR(r = 0.99, P < 0.001), respectively. The DVRs in the total myocardium region increased slightly as the size of FWHM increased and became stable at a Gaussian filter ≥6 mm. The secular equilibrium of SUVR was reached at around 50-min p.i. time. ConclusionThe DVR and R1 estimated from cardiac dynamic 18F-Florbetapir PET using pSRTM with kidney pseudo-reference tissue are suggested to quantify cardiac amyloid deposition and relative perfusion, respectively, in amyloidosis patients and healthy controls. We recommend a dual-phase scan: 0.5–5 min and 50–60 min p.i. as the appropriate time window for clinically assessing cardiac amyloidosis and perfusion measurements using 18F-Florbetapir PET.

Calculating Relative Lung Perfusion Using Fluoroscopic Sequences and Image Analysis: The Fluoroscopic Flow Calculator.

Maldistribution of pulmonary blood flow in patients with congenital heart disease impacts exertional performance and pulmonary artery growth. Currently, measurement of relative pulmonary perfusion can only be performed outside the catheterization laboratory. We sought to develop a tool for measuring relative lung perfusion using readily available fluoroscopy sequences. A retrospective cohort study was conducted on patients with conotruncal anomalies who underwent lung perfusion scans and subsequent cardiac catheterizations between 2011 and 2022. Inclusion criteria were nonselective angiogram of pulmonary vasculature, oblique angulation ≤20°, and an adequate view of both lung fields. A method was developed and implemented in 3D Slicer's SlicerHeart extension to calculate the amount of contrast that entered each lung field from the start of contrast injection and until the onset of levophase. The predicted perfusion distribution was compared with the measured distribution of pulmonary blood flow and evaluated for correlation, accuracy, and bias. In total, 32% (79/249) of screened studies met the inclusion criteria. A strong correlation between the predicted flow split and the measured flow split was found (R2=0.83; P<0.001). The median absolute error was 6%, and 72% of predictions were within 10% of the true value. Bias was not systematically worse at either extreme of the flow distribution. The prediction was found to be more accurate for either smaller and younger patients (age 0-2 years), for right ventricle injections, or when less cranial angulations were used (≤20°). In these cases (n=40), the prediction achieved R2=0.87, median absolute error of 5.5%, and 78% of predictions were within 10% of the true flow. The current study demonstrates the feasibility of a novel method for measuring relative lung perfusion using conventional angiograms. Real-time measurement of lung perfusion at the catheterization laboratory has the potential to reduce unnecessary testing, associated costs, and radiation exposure. Further optimization and validation is warranted.