5 mm slice gap); fluid attenuated inversion recovery (FLAIR) (TR/TE=9002/147

ms, 256×256 matrix, 240×240 mm FOV, 5 mm slice thickness, 1.5 mm slice gap); and gradient echo (T2⁎-weighted) (TR/TE=620/15 ms, flip angle α=20°, 240×180 mm FOV, 256×192 matrix, 5 mm slice thickness, 1 mm slice gap)]. DCE-MRI was performed using a 3D buy PR-171 fast spoiled gradient echo (FSPGR) sequence (TR/TE=8.1/3.2 ms, 240×240 mm FOV, 256×256 matrix, 4 mm slice thickness). The sequence was run before contrast agent administration with flip angles of 2° and 12° to facilitate T10 measurement [21], [22], [23], [24], [25] and [26], and the 12° acquisition was repeated 26 times with a temporal resolution of 69 s following an intravenous bolus injection of 40 ml gadodiamide (Omniscan, GE Healthcare, Chalfont St Giles, UK) into the antecubital vein. In order to assess scanner drift, the DCE-MRI protocol was also performed on six healthy volunteers without administration of contrast agent and on gadodiamide-doped water phantoms with T10 values representative of brain tissue and cerebrospinal fluid (CSF). An

experienced neuroradiologist examined the T2-weighted and FLAIR sequences from all patients in detail, classifying deep and periventricular white matter abnormalities according Afatinib supplier to the Fazekas scale (range 0 to 3) [27]. The scores for deep and periventricular abnormalities were averaged to give an overall Fazekas white matter rating and patients were dichotomized into those with overall Fazekas rating <1.5 (low) or ≥1.5 (high). The DCE-MRI data were motion corrected

by aligning all FSPGR acquisitions to the pre-contrast 12° acquisition using computational image realignment [28]. Maps of T10 were calculated voxel by voxel from the two pre-contrast acquisitions, Sa and Sb, acquired with flip angles αa=2° and αb=12° using the formula adapted from Brookes et al. [22] equation(1) 1T10=1TRln[SRsinαbcosαa−sinαacosαbSRsinαb−sinαa]where SR=Sa/Sb. Signal enhancement (Et) maps were calculated voxel by voxel for each of the 26 post-contrast time points t, such that Et=(St−S0)/S0, where S0 is the pre-contrast 12° acquisition. PAK5 The signal enhancement represents the fractional signal increase above baseline, such that a value of 0 represents no post-contrast signal increase and a value of 1 represents a doubling of post-contrast signal. Maps of contrast agent concentration Ct (in millimolars) were estimated from Et at each time point by voxel-by-voxel numerical solution of the formula given in Eq. ( 2) [29], equation(2) Et=exp(−r2CtTE)×[1−exp(−P−Q)−cosα2(exp(−P)−exp(−2P−Q))1−exp(−P)−cosα2(exp(−P−Q)−exp(−2P−Q))]−1where P=TR/T10 and Q=r1CtTR. This method makes the standard assumption that the post-contrast changes in R1 and R2⁎ are linearly related to Ct as determined by the contrast agent relaxivities r1 and r2.