"" of Cerebral Volume

JJA Marota, JB Mandeville, G Zaharchuk*, M Moskowitz, BR Rosen* Massachusetts General Hospital NMR Center, Charlestown, MA 02129

Introduction malized to the value at 115 mmHg. It is well established that near constant cerebral blood Results and Discussion flow (CBF) is maintained over a wide range of mean arte- There was little change in CBF between a MABP of 135 rial blood pressures (MABP), and only at extremes of pres- and 60 mmHg; mean value for CBF was 1. 37+0.11 ml/g/min. sure does CBF become pressure dependent [1]. This autoregu- Surprisingly, there was no change in CBV as determined ei- lation of CBF is accomplished by adjustment of cerebral ther by spin echo or by gradient echo images over this same to accomodate changes in pres- range of . As MABP decreased below 60 sure. As observed previously [2], cerebral vessels dilate to mmHg, CBF fell linearly (1.5 %change/mmHg); CBV did maintain flow as MABP falls; once maximally dilated, not decrease, however, until MABP fell below 30 mmHg in CBF falls with blood pressure. Thus, this mechanism sug- both gradient and spin echo acquired images. Furthermore, gests that cerebral blood volume (CBV) should increase as the percentage change in blood volume measured by spin resistance vessels dilate in response to a falling MABP. and gradient echo imaging began to diverge as CBF fell. At We have demonstrated that CBV can be accurately essentially no CBF, CBV had decreased by 60% and 38% for measured with high sensitivity using an exogenous T2 con- spin and gradient echo images, respectively. trast agent with a long blood half life [3]. Recently, we CBV did not increase during autoregulationof CBF. have developed a technique to simultaneously measure Therefore, vessel dilation associated with this process relative changes in CBV and absolute CBF by arterial spin must represent only a small fraction of total CBV, possibly labeling with use of a novel contrast agent [4]. In order to pre- sphincters [5]. These data support the notion test the hypothesis that CBV would increase as MABP de- that the main determinant of CBV is cerebral perfusion creases, we used these techniques to measure relative and, at least where flow is preserved, a simple model of changes in CBV and absolute CBF in brain during in- cerebral perfusion in which the major component of blood duced . Alternatively, if the magnitude of CBV volume is post arteriolar is adequate to describe the rela- were determined passively as a result of CBF, then total tionship between CBF and CBV [6]. The apparent mismatch volume would not change when flow remains constant even of CBV and CBF at low perfusionpressure may indicate an- in the face of decreasing perfusion pressure. other mechanism of vasodilationexists in low flow states. Methods The greater impact on spin echo signal indicates a potential Male Harlan Sprague-Dawley (225- 300gm) were differential role of small vessels in this process. This mis- anesthetized with halothane for tracheostomy and inser- match between flow and volume offers a potential for map- tion of femoral arterial and venous cannulae. Animals were ping areas of brain at risk for damage during stroke. maintained mechanically ventilated with 0. 6% halothane Conclusions in an air/oxygen mixture and paralyzed with pancuronium. Cerebral blood volume does not increase as a consequence of Arterial blood pressure was monitored throughout and ven- associated with the fall in cerebral vascular tilation adjusted to maintain normal arterial blood gases: resistance during autoregulationof CBF. Increased total and pH=7.39+0.01, PaCO2=39.5+1.4, PaO2=161+6. Temperature small vessel blood volume at low MABP suggests onset of was maintained at 38. 0+0.1 C with heating blankets. post-arteriolar vasodilation other than that associated MABP was decreased by controlled hemorrhage; arterial with control of CBF. blood was withdrawn with a syringe pump at 2-8 ml/hr. References For imaging, rats were placed in a cradle attached to a [1] Harper AM. J Neurol Neurosurg Psychiat.1966;29:398- plastic stereotactic head frame. In two animals, relative 403 CBV and absolute CBF were simultaneously measured at 4.7 [2] Kontos HA, et al. Am J Physiol. 1978; 234:H371-H383 T, as described [4]. Briefly, a novel contrast agent (MPEG- [3] Mandeville JB, et. al. Magn Res Med. 1998; in press. PL-DyDTPA, 0.15 mmol Dy/kg) with a high AX/AR1 ratio [4] Zaharchuk G, et al. Proc Mag Res Med. 1998; submitted was used to measure relative CBV using gradient and spin echo steady-state susceptibility contrast and CBF using ar- [5] Paulson OB, et al. Cerebrovasc Brain Metab Rev. 1990; terial spin labeling (TR/TE = 2000/3.7 ms). In two addi- 2:161 tional rats, total and microvascular CBV weighted images [6] Mandeville JB, et al. Proc Mag Res Med. 1998; submitted of rat brain were obtained at 2 T using interleaved gradient 20 and spin echo planar imaging, respectively. Dextran coated ...... superparamagnetic monocrystaline iron oxide nanoparticle 003 was injected at 14 mg/kg in order to determined percent C> - 40 - , CBV change as previously described [3]; TR/TE: 5000/25 - " and TR/TE: 5000/60 for gradient and spin echo, respec- -60 ] - .. -. CBV.(GE) n=4.| tively. -80 1 . 4 . . ..Io----CBF-CBV (SE)n= n=2 | Absolute values for CBF were calculated from a whole brain slice ROI at different MABP and averaged; to calcu- - 100 late percentage change in CBF, these values were normal- 0 20 40 60 80 100 120 140 ized to absolute flow at 115 mmHg. Similarly, the relative MABP (mm Hg) change in CBV was calculated at different MABP for spin and gradient echo sequences from echo planar and CAPTIVE Fig 1. Percent change in CBF and CBV measured by spin imaging and averaged; relative changes in CBV were nor- (SE] and gradient (GE) echo, during induced hypotension.