Figure 1.
Outline of the hyperpolarized 129Xe gas delivery to the ex vivo lung.
(A) Experimental ex vivo setup with hp 129Xe administered from a balloon reservoir chamber into the storage volume (VB) before being inhaled by the lung. The lung is caused to inhale (exhale) by the negative (positive) external ‘pleural’ pressure applied via the suction volume (Vs) from the ventilation syringe upon the artificial pleural cavity; (B) Ex vivo lung submerged with its orifice down (sutured to a cannula) in 5% glucose solution within the ventilation chamber with its posterior-anterior axis aligned in z-direction. In this sketch, a negative pleural pressure caused by Vs leads to a partial inflation of the ex vivo lung, inhaling a selected gas (hp 129Xe, or N2 or O2) from the storage volume VB. Drugs are administered via a cannula sited in the right ventricle with the excess fluid outlet located below the fluid level in the chamber. All resulting MR images shown in subsequent figures are depicted with the lung orifice pointing upwards.
Table 1.
Relationship between syringe suction volume and inhaled gas volume1.
Table 2.
Experimentally determined ex vivo lung residual volumes (RV) 1.
Figure 2.
Non-slice selective coronal VFA FLASH MR images used for calculation of residual volume (RV).
(A) Acquired after inhalation to Vs = 5 mL (actual inhalation, Vi = 3.09 mL); (B) Inhalation to Vs = 5 mL followed by full exhalation to Vs = 0 mL (Vi = 0 mL) before the MR image is acquired. Image resolution is 128×64 with FOV = 46.9 mm in the longitudinal and FOV = 30.0 mm in the axial dimensions, respectively. In this presentation, the orifice of the lung is pointing up with the posterior-anterior axis aligned with the z-direction.
Figure 3.
Hyperpolarized 129Xe gas distribution on increasing inhalation volumes.
Non-slice selective coronal VFA FLASH images as a function of increasing suction volume (Vs) (and inhaled volume (Vi)). The corresponding histograms displaying integrated intensities, , for each row, m, are shown to the right of the images. The vertical axis of the image is parallel to the direction of the Bo field (z-direction) and corresponds to the posterior-anterior axis (base to apex) of the lung in the magnet. Phase encoding is applied transverse to the Bo field direction. As the suction volume increases from 0.5 mL to 6.0 mL the image contrast is greatly enhanced. The effect is caused by the increasing quantities of inhaled hp gas contained in the lung as the suction volume rises. Matrix 128×64 with FOV = 46.9×30.0 mm2.
Figure 4.
Normalization of hyperpolarized 129Xe distribution by total signal intensity and position along the anterior-posterior axis.
(A) Integrated signal intensity (taken from Fig. 3) in arbitrary units (a.u.) as a function of the image row number m (in z-direction); (B) Integrated signal intensity after normalization by the total signal intensity (i.e. the integrated intensity of all voxels, , of the respective MR image); (C) Normalized integrated signal intensity as in (B) but as a function of position along the lung posterior-anterior axis (z-axis) from base to apices. Independent of inhalation volume and actual lung expansion, the 0.0 point refers the base of the lung, whereas 1.0 refers to the apices. The 50% signal intensity position in the lungs is indicated by grey vertical line (C) i.e. 50% of the total signal intensity lies to both sides of the grey line.
Figure 5.
Timed release of hyperpolarized 129Xe during constant inhalation volumes.
Coronal slice selective VFA FLASH images for directed ventilation schemes with a histogram that displays the integrated intensities in each row are shown to the right of the images. Scheme 1 (A–C)- initial inhalation consists of a known volume of hp gas, Vs(hp), followed by dark gas, Vs(Dark). Scheme 2 (D–E)- the reversal with the inhalation of Vs(Dark) followed by Vs(hp). Full 5.0 mL inhalation of hp gas with edge detection using Kirsch operator [71] with window level adjusted to show lower signal intensities (F). Z-axis along Bo in posterior-anterior axis (base to apex) of the lung in the magnet and x-axis along indirect (phase encoding) dimension. Imaging parameters: 4 mm central slice, matrix 128×64, FOV = 46.9×30.0 mm2. Positioning of the lung as in Fig. 2.
Figure 6.
Airway responsiveness testing in an excised rat lung.
Slice selective VFA FLASH images of positively responding ex vivo rat lungs after intravenous challenges of 60 µg methacholine with subsequent reversal produced by flushes of intravenous 5% glucose and 1000 µg salbutamol. Images were performed using a constant inhalation syringe (suction) volume of VS = 5 mL. Imaging parameters: 4 mm central slice, matrix 128×64, FOV = 46.9×30.0 mm2. Positioning of the lung as in Fig. 2.
Figure 7.
Airway responsiveness testing in an excised guinea pig lung.
Slice-selective VFA FLASH images of ex vivo guinea pig lungs after intravenous challenges with 5% glucose solution alone and 10 µg methacholine. Subsequent reversal was produced by flushes of intravenous 5% glucose and 200 µg salbutamol. Images were performed with a constant inhalation syringe (suction) volume of VS = 5 mL. Imaging parameters: 4 mm central slice, matrix 128×64, FOV = 46.9×30.0 mm2. Positioning of the lung as in Fig. 2.