V alidation o f the ASL techniques

The validation of regional perfusion values with corresponding values obtained using other flow m easurem ent techniques in the same subject, has only been perform ed to a lim ited degree and solely for the continuous labelling technique (W alsh, 1994; Ye, 1997b; H ernandez, 1998). The attem pted validation of any perfusion technique is

com plicated by the absence o f an accepted, gold standard m ethod. The different

m ethods listed in Table 2.2, m ay not all m easure exactly the same quantity by virtue of their differing theoretical foundations and m ethodologies. N evertheless, useful inform ation can be gained by com paring the values obtained from different techniques. This section describes two such com parative investigations.

3.8.1 FAIR a n d CASL 3.8.1.1 Methods

The continuous and pulsed (FAIR) variants of the A SL techniques were im plem ented in tandem on a coronal 2.3 mm slice in the rat (n=2). In one of the two anim als, an M CA

C h a p te r 3 P erfu sio n

occlusion had been induced by the conventional intralum inal suture method. All experim ents were carried out on the 2.35T system with EPI-based sequences. Both F A IR and continuous pulse sequences incorporated bipolar gradients (b = 10 mm^/sec) in order to reduce the effects of intravascular contam ination.

FAIR-. Selective and non-selective images were obtained at 8 T I delays (TI = 200-3500 m s, T R = 8 sec, N EX = 25, im aging slth = 2.3 mm, inversion slth = 6 mm, spin-echo E P I acquisition). Other details of the sequence were as described in Section 4.4.2. The transit time was taken into consideration by assum ing a constant value o f 100 ms for the pulsed experim ent, and the m odified biexponential expression (Eq. [A2]) was em ployed for quantification.

CASL technique-. The Ti in the presence of off-resonance irradiation, Tisat, was m easured using the method described in Section 3.5.3.2. The off-resonance pulse length, T, was varied in 8 steps ( t = 200-3500 ms, Acû = 5 kHz, TR = 10 sec, spin-echo E P I acquisition). The spin-tagging control and tagged experim ents em ployed the same spin-echo EPI acquisition sequence (x = 6 sec, tagging RF am plitude = 70 mG, tagging gradient = ±140 H z/m m , Ao) = 5 kHz, post-labelling delay(w )=100 ms, N EX = 64, TR = 10 sec). The frequency offset corresponded to a tagging plane in the neck that was 18 m m from the im aging slice. The transit times are, therefore, expected to be significant and m ust be included in the analysis (Eq. [3.15]). Values of Ôa = 200 ms and 5 = 600 ms w ere chosen (see Section 3.5.3.2) from the results of previous experim ents and reported data (Alsop, 1996; Ye, 1997a).

3.8.1.2 Image and data analysis

C B F maps were created on a pixel-by-pixel basis. Regions were draw n in the cortical and striatal regions in each cerebral hem isphere. In the occluded animal, an R O I was placed in the ischaemic area (as determ ined from a pilot diffusion-w eighted scan) and the analysis of this region was treated separately. Regions contained approxim ately 200 pixels; statistical analysis could not be perform ed on this data due to the lim ited num ber o f experim ents carried out thus-far.

3 .8 .1.3 Results and Discussion

T he average non-occluded perfusion values were as follow s (with SDs within the individual regions not quoted):

C h a p te r 3 P e rfu sio n

FAIR:

101 ml/lOOg/min and 141 ml/lOOg/min in cortex and striatum respectively (A nim al 1) 144 ml/lOOg/min and 151 ml/lOOg/min in cortex and striatum respectively (A nim al 2)

CASL:

101 ml/lOOg/min and 151 ml/lOOg/min in cortex and striatum respectively (A nim al 1) 118 ml/lOOg/min and 150 ml/lOOg/min in cortex and striatum respectively (A nim al 2)

In the occluded cortical region, the CBF was 19 ml/lOOg/min (FAIR) and 4 ml/lOOg/min (CASL).

The CBF values in the unoccluded regions as m easured by the two techniques were in good agreement. The C A SL m easurem ents in the occluded area appear to underestim ate the corresponding FA IR values (values approxim ately 80% low er than the FAIR m easurem ents) and this may reflect the greater transit time sensitivity o f the form er technique. The transit tim e insensitivity of the continuous technique had not been optim ised since the chosen post-labelling delay (w=100 ms) was considerably sm aller than the tissue transit time. The CBF m easurem ents were, therefore, sensitive to the chosen values of ôa and Ô. Further experim ents are required in order to confirm this observed underestim ation.

3.8.2 FAIR an d Hydrogen (Hz) clearance

H ydrogen clearance is a com m only used polarographic technique for the m easurem ent of blood flow under a wide variety of experim ental conditions (see Table 2.2; Young, 1980). Positively polarised electrodes inserted into tissue oxidise inhaled hydrogen and provide an acceptor surface for the electrons. The subsequent flow o f current is norm ally in the order of nanoam peres (nA) and is detected by an electrode im pedance m easuring system. The relatively inexpensive technique allows m ultiple flow m easurem ents over long periods of time unlike autoradiography or m icrosphere

methods. In this study, FA IR and H2 clearance measurem ents were com pared in the

gerbil. This work was carried out in conjunction with Dr. E. Proctor o f the Royal College of Surgeons, London.

C h a p te r 3 P e rfu sio n

3.8.2.1 Methods

FAIR: The FA IR technique was im plem ented on the 2.35T system in the m anner described previously in this chapter and in Section 4.4.2. Both the long TR (biexponential fit) and the short TR single subtraction im plem entations of FA IR were em ployed in various com binations (see Section 4.4). The coronal slice (slth=2.3 mm) was positioned between the frontal and parietal electrode positions. The electrode positions were slightly visible in the spin-echo EPI images as partial volum e and through-slice susceptibility effects but the placem ent o f the ROIs avoided this area.