Inhaled Xenon Washout as a Biomarker of Alzheimer’s Disease

Biomarkers have the potential to aid in the study of Alzheimer’s disease (AD); unfortunately, AD biomarker values often have a high degree of overlap between healthy and AD individuals. This study investigates the potential utility of a series of novel AD biomarkers, the sixty second 129Xe retention time, and the xenon washout parameter, based on the washout of hyperpolarized 129Xe from the brain of AD participants following inhalation. The xenon washout parameter is influenced by cerebral perfusion, T1 relaxation of xenon, and the xenon partition coefficient, all factors influenced by AD. Participants with Alzheimer’s disease (n=4) and healthy volunteers (n=4) were imaged using hyperpolarized 129Xe magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to determine the amount of retain xenon in the brain. At 60 sec post breath hold, AD patients retained significantly higher amounts of 129Xe compared to healthy controls. Data was fit to a pharmacokinetic model and the xenon washout parameter was extracted. Xenon washout in white and grey matter occurs at a slower rate in Alzheimer’s participants (129Xe half-life time of 42s and 43s, respectively) relative to controls (20s and 16s, respectively). Following larger scale clinical trials for validation, the xenon washout parameter has the potential to become a useful biomarker for the support of an AD diagnosis.

Washout of 133-Xenon as an Objective Assessment of Paranasal Sinus Ventilation in Endoscopic Sinus Surgery

Endoscopic sinus surgery (ESS) is today a common method for the treatment of chronic rhinosinusitis. Assessment of the results has been based mainly upon subjective evaluation, and only a few reports present objective measurements. In the present study, the 133-xenon washout technique was used for preoperative and postoperative evaluation of paranasal sinus ventilation in 12 patients selected for ESS. The postoperative half-times (T1/2) of 133-xenon washout were lower in the sinuses with abnormal preoperative half-times (T1/2), especially in the maxillary sinuses, where the postoperative T1/2 was 44 (22 to 150) minutes (median and quartiles, Q1–Q3) as compared with a preoperative T1/2 of 202 (94 to 278) minutes. The postoperative evaluation included a questionnaire and a follow-up visit with endoscopy and measurements of nasal nitric oxide. The results showed that patients who declared a marked reduction in symptoms exhibited significantly improved sinus ventilation. However, no direct correlation was found between improvement in ventilation and symptom improvement. Nine of the 12 patients showed improvement on endoscopy, and these patients also exhibited improved sinus ventilation. The postoperative nasal nitric oxide levels were within the normal range in 11 of the 12 patients; the other patient showed pathological T1/2 values for all paranasal sinuses. The 133-xenon washout technique is thus a method that can be used for objective evaluation of the ventilation of the paranasal sinuses before and after ESS procedures. However, the technique cannot be used to evaluate sinuses with totally obstructed ostia or postoperative sinuses with very wide neo-ostia, as rapid washout may lead to no activity remaining at the time of measurement.

Continuous Arterial PO(2) and PCO(2) Measurements in Swine during Nitrous Oxide and Xenon Elimination

Background During nitrous oxide (N2O) elimination, arterial oxygen tension (PaO2) decreases because of the phenomenon commonly called diffusive hypoxia. The authors questioned whether similar effects occur during xenon elimination. Methods Nineteen anesthetized and paralyzed pigs were mechanically ventilated randomly for 30 min using inspiratory gas mixtures of 30% oxygen and either 70% N2O or xenon. The inspiratory gas was replaced by a mixture of 70% nitrogen and 30% oxygen. PaO2 and carbon dioxide tensions were recorded continuously using an indwelling arterial sensor. Results The PaO2 decreased from 119+/-10 mm Hg to 102+/-12 mm Hg (mean+/-SD) during N2O washout (P<0.01) and from 116+/-9 mm Hg to 110+/-8 mm Hg during xenon elimination (P<0.01), with a significant difference (P<0.01) between baseline and minimum PaO2 values (deltaPaO2, 17+/-6 mm Hg during N2O washout and 6+/-3 mm Hg during xenon washout). The PaCO2 value also decreased (from 39.3+/-6.3 mm Hg to 37.6+/-5.8 mm Hg) during N2O washout (P<0.01) and during xenon elimination (from 35.4+/-1.6 mm Hg to 34.9+/-1.6 mm Hg; P< 0.01). The deltaPaCO2 was 1.7+/-0.9 mm Hg in the N2O group and 0.5+/-0.3 mm Hg in the xenon group (P<0.01). Conclusion Diffusive hypoxia is unlikely to occur during recovery from xenon anesthesia, probably because of the low blood solubility of this gas.

The 57 mm Thermal Clearance Probe: A Non-Invasive Tool for Measuring Subcutaneous Blood Flow

1. The segmented thermal clearance probe is a noninvasive instrument which measures heat thermal clearance, a variable directly proportional to superficial blood flow, with a depth sensitivity theoretically proportional to the sensor diameter. We compared an 18 mm sensor and a recently developed 57 mm sensor with the reference technique of xenon washout. 2. The theoretical depth sensitivity of the sensors was assessed using Perspex spacers. Ninety-five per cent of sensitivity had been lost at the respective depths of 3.5 mm and 7.1 mm for the 18 mm and 57 mm sensors. 3. A comparison was made between heat thermal clearance reading and 133Xe decay curves using the two probes for 15 min after injection of 133Xe at 2 mm and 6 mm depths in the anterior thigh in 41 subjects. The 57 mm sensor showed similar correlation with xenon washout at 2 mm injection depth (r = 0.89) and 6 mm injection depth (r = 0.86), whereas the 18 mm sensor showed greater correlation at 2 mm (r = 0.92) than at 6 mm (r = 0.62). 4. The 57 mm sensor was compared with xenon washout at 6 mm in eight insulin-treated diabetic subjects. The relationship was similar to that in non-diabetic subjects (r = 0.79), with no significant difference in slope or intercept. 5. It is concluded that the 57 mm thermal clearance probe may be used to study blood flow at the depth of insulin injection (6 mm) in diabetic and non-diabetic subjects.