OMNI: Gas Chromatograph Captures Seven Common PET Radiotracer Analytes in under 5 Minutes.

A novel gas chromatography method was developed using automatic injections to identify and quantify the amount of residual solvents or analytes in samples of fluorine-18 and carbon-11 radiopharmaceuticals. This approach evaluates seven analytes in less than 5 versus 13 min of acquisition time. The method additionally includes a 3 min bakeout to aid in the removal and carry-over of higher-boiling impurities. Chromatographic parameters such as column temperature, hold time, column pressure, flow rate, and split ratios were adjusted and optimized to analyze radioactive drug samples containing analytes which include methanol, ethanol, acetone, acetonitrile, triethylamine, N,N-dimethylformamide, and dimethyl sulfoxide. The relative standard deviation for each solvent was determined to be no greater than 1.6%. The method limit of detection (LOD) and limit of quantification (LOQ) were between 0.053 and 0.163 and 0.000 (5.791 × 10-6) and 0.520 mg/mL, respectively. This GC technique, using flame ionization detection (FID), was validated and is currently employed for the routine quality control of all approved IND and RDRC PET radiopharmaceuticals at our center.

Cognition and Cerebral Blood Flow After Extracranial Carotid Revascularization for Carotid Atherosclerosis: A Systematic Review.

PURPOSE: Extracranial atherosclerotic carotid stenosis is associated with inadequate cerebral blood flow (CBF) and cognitive dysfunction. The impact of extracranial carotid revascularization on cognition and how any cognitive change relates to changes in CBF are less clear. This review examines the effects of revascularization of extracranial carotid disease by carotid endarterectomy (CEA) or carotid stenting (CAS) on cognition, and how this relates to changes in CBF. METHODS: A systematic review of existing reports in the Medline, Embase, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement recommendations. All original retrospective or prospective studies and clinical trials that compared pre- and postoperative cognitive function and CBF in patients with extracranial carotid stenosis who underwent CEA or CAS versus a control group, published between January 1985 and December 2022, were identified and considered eligible for inclusion in this study. FINDINGS: Seven studies (661 participants; 460 CEA or CAS) were identified. All were observational studies and of moderate to good methodologic quality. Six studies (619 participants; follow-up range 1 month to 2 years) demonstrated improvement in some cognitive domains following CEA or CAS, improvement in CBF following revascularization, and correlated some of these cognitive changes with changes in CBF. One study (42 participants; 3 months follow-up) found cognitive improvement following CEA, but found no improvement in CBF or any correlation between cognitive and CBF change. The literature however represented heterogenous study populations examining asymptomatic and/or symptomatic carotid stenosis, differing in treatment modality and criteria for control groups ranging from healthy volunteers to those with stenosis but not who underwent surgical revascularization, and finally, differing reporting methods. This heterogeneity precluded meta-analysis. IMPLICATIONS: Definitive conclusions are limited by variation in cognitive function assessment, timing of testing, and how these are correlated to CBF. However, research suggests a potential improvement in cognition which may be associated with improvement in CBF, particularly in those patients who have more significant CBF deficit at baseline. Further studies are required to better understand this association and provide a clearer picture of the cognitive effects of carotid revascularization.

Zenith AAA endovascular graft suprarenal bare metal stent separation with graft migration and type IA endoleak.

BACKGROUND: The Zenith endovascular graft (Cook Medical, Bloomington, IN, USA) is a well-recognised device used in endovascular repair of abdominal aortic aneurysms (EVAR). After a small number of reported cases of suprarenal stent separation from the main body of the graft, modifications were made to the strength and durability of the suture line attachment of the proximal bare metal component prior to release in 2003. This report describes a further case of suprarenal stent separation and type IA endoleak in a patient who underwent an EVAR using the Zenith device in 2012. METHODS: We present a case report of a 77-year-old male with incidental finding of type IA endoleak on a background of elective endovascular repair for 50.4-mm infrarenal abdominal aortic aneurysm (AAA), with a Cook Zenith endograft. Computed tomography (CT) demonstrated separation of the suprarenal bare metal stent from the main body of the endograft, with resultant graft migration and increase in native aneurysm sac size. RESULTS: The patient underwent semi-urgent surgery with successful placement of a bridging thoracic stent graft between the lowest renal artery and main body of the pre-existing graft. CONCLUSIONS: This case report describes a rare complication of Zenith devices, additionally emphasising the importance of regular surveillance imaging following EVAR.

Aortic graft explants - A single institution analysis of incidence and outcomes.

OBJECTIVES: Explantation of both endovascular endovascular aneurysm repair and open aortic grafts is a procedure associated with high peri-operative risk, and the current study sought to determine the outcomes and trends over time in these patients. METHODS: This study examined data from all patients undergoing explant of an aortic graft (both open and endovascular) between January 2004 and December 2020 at a single centre. Variables analysed included comorbidities, duration to and indication for explantation, type of revascularization, in-hospital complications and mortality, duration of hospital and ICU stay, and out-patient mortality. RESULTS: Of 688 open and 1352 EVARs performed, 46 patients underwent 48 explants. Five were open grafts and 43 were endografts, equating to an explant rate of 0.73% of open and 3.18% EVARs. Average time to explant was 70 months, with patients presenting electively having a significantly longer duration to representation than those presenting emergently (51 vs 44 months, p=0.003). Indication for explant was endoleak in 70%, infection in 23%, and occlusion in 6%. Of the endoleaks, 61% of were Type 1, 22% Type II, 11% Type IV, and 6% Type V. On representation, 17 patients (35%) were symptomatic. Overall mortality rate was 8.3%, with a trend for higher mortality in emergent than elective presentations (11.8 vs 6.5%, p=0.55). There was no change in explant rate over time. CONCLUSIONS: Elective aortic graft explantation is associated with low mortality, despite its complexity and patient comorbidities. Patients presenting with symptoms suffered higher mortality and a longer post-operative course, suggesting that aortic graft explantation should be considered sooner rather than later, rather than persisting with repeated endovascular management.

Near infrared spectroscopy in peripheral artery disease and the diabetic foot: A systematic review.

With the need for tools that assess microvascular status in diabetic foot disease (DFD) being clear, near infrared spectroscopy (NIRS) is a putative method for noninvasive testing of the diabetic foot. The use of NIRS in patients with peripheral arterial disease (PAD) has extended to its role in studying the pathophysiology of DFD. NIRS generates metrics such as recovery time, deoxygenation, oxygen consumption (VO2 ), tissue oxygen saturation (StO2 ), total haemoglobin (HbT), and oxyhaemoglobin area under the curve (O2 HbAUC ). NIRS may potentially help the multidisciplinary team stratify limbs as high-risk, especially in diabetic patients with symptoms masked by peripheral neuropathy. NIRS may be useful for assessing treatment effectiveness and preventing deterioration of patients with PAD.

Hybrid Repair of a Persistent Sciatic Artery Aneurysm.

Persistent sciatic arteries are rare congenital abnormalities, with an incidence between .01-.6%. Whilst most patients with the pathology are asymptomatic during their younger years, up to 48% of patients will suffer aneurysmal degeneration of the persistent sciatic artery and present with claudication or lower limb ischaemia (from distal embolisation of mural thrombus). Due to the rare nature of persistent sciatic artery aneurysms, optimal management of the pathology is yet to be determined. Both endovascular and open techniques have been described in the management of this pathology, however hybrid management approaches are reported infrequently. The authors present a case of a persistent sciatic artery aneurysm successfully treated in a 69-year-old male utilising a hybrid approach with a femoropopliteal bypass (below knee), Amplatzer plug occlusion of the aneurysm and subsequent resection of the aneurysm.

Real-Time Positron Emission Tomography Evaluation of Topotecan Brain Kinetics after Ultrasound-Mediated Blood-Brain Barrier Permeability.

Glioblastoma (GBM) is the most common primary adult brain malignancy with an extremely poor prognosis and a median survival of fewer than two years. A key reason for this high mortality is that the blood-brain barrier (BBB) significantly restricts systemically delivered therapeutics to brain tumors. High-intensity focused ultrasound (HIFU) with microbubbles is a methodology being used in clinical trials to noninvasively permeabilize the BBB for systemic therapeutic delivery to GBM. Topotecan is a topoisomerase inhibitor used as a chemotherapeutic agent to treat ovarian and small cell lung cancer. Studies have suggested that topotecan can cross the BBB and can be used to treat brain metastases. However, pharmacokinetic data demonstrated that topotecan peak concentration in the brain extracellular fluid after systemic injection was ten times lower than in the blood, suggesting less than optimal BBB penetration by topotecan. We hypothesize that HIFU with microbubbles treatment can open the BBB and significantly increase topotecan concentration in the brain. We radiolabeled topotecan with 11C and acquired static and dynamic positron emission tomography (PET) scans to quantify [11C] topotecan uptake in the brains of normal mice and mice after HIFU treatment. We found that HIFU treatments significantly increased [11C] topotecan brain uptake. Moreover, kinetic analysis of the [11C] topotecan dynamic PET data demonstrated a substantial increase in [11C] topotecan volume of distribution in the brain. Furthermore, we found a decrease in [11C] topotecan brain clearance, confirming the potential of HIFU to aid in the delivery of topotecan through the BBB. This opens the potential clinical application of [11C] topotecan as a tool to predict topotecan loco-regional brain concentration in patients with GBMs undergoing experimental HIFU treatments.

VADER: a variable dose-rate external 137Cs irradiator for internal emitter and low dose rate studies.

In the long term, 137Cs is probably the most biologically important agent released in many accidental (or malicious) radiation disasters. It can enter the food chain, and be consumed, or, if present in the environment (e.g. from fallout), can provide external irradiation over prolonged times. In either case, due to the high penetration of the energetic γ rays emitted by 137Cs, the individual will be exposed to a low dose rate, uniform, whole body, irradiation. The VADER (VAriable Dose-rate External 137Cs irradiatoR) allows modeling these exposures, bypassing many of the problems inherent in internal emitter studies. Making use of discarded 137Cs brachytherapy seeds, the VADER can provide varying low dose rate irradiations at dose rates of 0.1 to 1.2 Gy/day. The VADER includes a mouse "hotel", designed to allow long term simultaneous residency of up to 15 mice. Two source platters containing ~ 250 mCi each of 137Cs brachytherapy seeds are mounted above and below the "hotel" and can be moved under computer control to provide constant low dose rate or a varying dose rate mimicking 137Cs biokinetics in mouse or man. We present the VADER design and characterization of its performance over 18 months of use.

Visualizing and quantifying cutaneous microvascular reactivity in humans by use of optical coherence tomography: impaired dilator function in diabetes.

The pathophysiology and time course of impairment in cutaneous microcirculatory function and structure remain poorly understood in people with diabetes, partly due to the lack of investigational tools capable of directly imaging and quantifying the microvasculature in vivo. We applied a new optical coherence tomography (OCT) technique, at rest and during reactive hyperemia (RH), to assess the skin microvasculature in people with diabetes with foot ulcers (DFU, n = 13), those with diabetes without ulcers (DNU, n = 9), and matched healthy controls (CON, n = 13). OCT images were obtained from the dorsal part of the foot at rest and following 5 min of local ischemia induced by inflating a cuff around the thigh at suprasystolic level (220 mmHg). One-way ANOVA was used to compare the OCT-derived parameters (diameter, speed, flow rate, and density) at rest and in response to RH, with repeated-measures two-way ANOVA performed to analyze main and interaction effects between groups. Data are means ± SD. At rest, microvascular diameter in the DFU (84.89 ± 14.84 µm) group was higher than CON (71.25 ± 7.6 µm, P = 0.012) and DNU (71.33 ± 12.04 µm, P = 0.019) group. Speed in DFU (65.56 ± 4.80 µm/s, P = 0.002) and DNU (63.22 ± 4.35 µm/s, P = 0.050) were higher than CON (59.58 ± 3.02 µm/s). Microvascular density in DFU (22.23 ± 13.8%) was higher than in CON (9.83 ± 2.94%, P = 0.008), but not than in the DNU group (14.8 ± 10.98%, P = 0.119). All OCT-derived parameters were significantly increased in response to RH in the CON group (all P < 0.01) and DNU group (all P < 0.05). Significant increase in the DFU group was observed in speed (P = 0.031) and density (P = 0.018). The change in density was lowest in the DFU group (44 ± 34.1%) compared with CON (199.2 ± 117.5%, P = 0.005) and DNU (148.1 ± 98.4, P = 0.054). This study proves that noninvasive OCT microvascular imaging is feasible in people with diabetes, provides powerful new physiological insights, and can distinguish between healthy individuals and patients with diabetes with distinct disease severity.

Optical coherence tomography: a novel imaging approach to visualize and quantify cutaneous microvascular structure and function in patients with diabetes.

INTRODUCTION: The pathophysiology of microvascular disease is poorly understood, partly due to the lack of tools to directly image microvessels in vivo. RESEARCH DESIGN AND METHODS: In this study, we deployed a novel optical coherence tomography (OCT) technique during local skin heating to assess microvascular structure and function in diabetics with (DFU group, n=13) and without (DNU group, n=10) foot ulceration, and healthy controls (CON group, n=13). OCT images were obtained from the dorsal foot, at baseline (33°C) and 30 min following skin heating. RESULTS: At baseline, microvascular density was higher in DFU compared with CON (21.9%±11.5% vs 14.3%±5.6%, p=0.048). Local heating induced significant increases in diameter, speed, flow rate and density in all groups (all p<0.001), with smaller changes in diameter for the DFU group (94.3±13.4 µm), compared with CON group (115.5±11.7 µm, p<0.001) and DNU group (106.7±12.1 µm, p=0.014). Heating-induced flow rate was lower in the DFU group (584.3±217.0 pL/s) compared with the CON group (908.8±228.2 pL/s, p<0.001) and DNU group (768.8±198.4 pL/s, p=0.014), with changes in density also lower in the DFU group than CON group (44.7%±15.0% vs 56.5%±9.1%, p=0.005). CONCLUSIONS: This proof of principle study indicates that it is feasible to directly visualize and quantify microvascular function in people with diabetes; and distinguish microvascular disease severity between patients.

Binding of the D3-preferring antipsychotic candidate F17464 to dopamine D3 and D2 receptors: a PET study in healthy subjects with [11C]-(+)-PHNO.

RATIONALE: F17464, a dopamine D3 receptor antagonist with relatively high D3 selectivity (70 fold vs D2 in vitro), exhibits an antipsychotic profile in preclinical studies, and therapeutic efficacy was demonstrated in a randomized placebo-controlled clinical trial in patients with schizophrenia (Bitter et al. Neuropsychopharmacology 44(11):1917-1924, 2019). OBJECTIVE: This open-label study in healthy male subjects aimed at characterizing F17464 binding to D3/D2 receptors and the time course of receptor occupancy using positron emission tomography (PET) imaging with a D3-preferring tracer, [11C]-(+)-PHNO. METHODS: PET scans were performed at baseline and following a single 30 mg or 15 mg dose of F17464 (3 subjects/dose), and blood samples were collected for pharmacokinetic analysis. Receptor occupancy was calculated based upon reduction in binding potential of the tracer following F17464 administration. The relationship between plasma F17464 concentration and D3/D2 receptor occupancy was modeled and the plasma concentration corresponding to 50% receptor occupancy (EC50) calculated. RESULTS: Both doses of F17464 robustly blocked [11C]-(+)-PHNO D3 receptor binding, with substantial occupancy from 1 h post-administration, which increased at 6-9 h (89-98% and 79-87% for the 30 mg and 15 mg groups, respectively) and remained detectable at 22 h. In contrast, D2 binding was only modestly blocked at all time points (< 18%). F17464 exhibited a combination of rapid peripheral kinetics and hysteresis (persistence of binding 22 h post-dose despite low plasma concentration). The best estimate of the EC50 was 19 ng ml-1 (~ 40 nM). CONCLUSION: Overall, F17464 was strongly D3-selective in healthy volunteers, a unique profile for an antipsychotic candidate drug.

A Technique of "Chimney Nellix" for the Management of Type 1a Endoleak After EVAR.

This report presents 3 procedures with visceral "chimney stenting" in conjunction with an endovascular aneurysm sealing (EVAS) device, known as chEVAS, for treatment of type 1a endoleak. It includes the first published chEVAS in a patient with previous fenestrated endovascular aneurysm repair (FEVAR). Cases include an 80-year-old man 8 years after FEVAR for a juxtarenal abdominal aortic aneurysm (AAA); an 85-year-old woman 9 months after endovascular aneurysm repair (EVAR) for a ruptured infrarenal AAA; and an 84-year-old woman 3 months after EVAR for a symptomatic infrarenal AAA. Technical success was achieved in all cases, with 1 postoperative death. The remaining 2 patients had no residual type 1a endoleak at 10 and 14 months respectively.

Complications in the management of metastatic spinal disease.

Metastatic spine disease accounts for 10% to 30% of new cancer diagnoses annually. The most frequent presentation is axial spinal pain. No treatment has been proven to increase the life expectancy of patients with spinal metastasis. The goals of therapy are pain control and functional preservation. The most important prognostic indicator for spinal metastases is the initial functional score. Treatment is multidisciplinary, and virtually all treatment is palliative. Management is guided by three key issues; neurologic compromise, spinal instability, and individual patient factors. Site-directed radiation, with or without chemotherapy is the most commonly used treatment modality for those patients presenting with spinal pain, causative by tumours which are not impinging on neural elements. Operative intervention has, until recently been advocated for establishing a tissue diagnosis, mechanical stabilization and for reduction of tumor burden but not for a curative approach. It is treatment of choice patients with diseaseadvancement despite radiotherapy and in those with known radiotherapy-resistant tumors. Vertebral resection and anterior stabilization with methacrylate or hardware (e.g., cages) has been advocated.Surgical decompression and stabilization, however, along with radiotherapy, may provide the most promising treatment. It stabilizes the metastatic deposited areaand allows ambulation with pain relief. In general, patients who are nonambulatory at diagnosis do poorly, as do patients in whom more than one vertebra is involved. Surgical intervention is indicated in patients with radiation-resistant tumors, spinal instability, spinal compression with bone or disk fragments, progressive neurologic deterioration, previous radiation exposure, and uncertain diagnosis that requires tissue diagnosis. The main goal in the management of spinal metastatic deposits is always palliative rather than curative, with the primary aim being pain relief and improved mobility. This however, does not come without complications, regardless of the surgical intervention technique used. These complication range from the general surgical complications of bleeding, infection, damage to surrounding structures and post operative DT/PE to spinal specific complications of persistent neurologic deficit and paralysis.