Timing of CT Perfusion abnormalities within and around spontaneous intracerebral hemorrhage during the transition from acute to subacute phases Enrico Fainardi1, Vania Ramponi2, Gloria Roversi3, Massimo Borrelli1, Andrea Saletti1, Andrea Bernardoni1, Carmine Tamborino3, Francesco Di Biase2, Alessandro De Vito3, Michele Cavallo2, Stefano Ceruti1, Riccardo Tamarozzi1 1Unità Operativa di Neuroradiologia, 2Unità Operativa di Neurochirurgia, 3Unità Operativa di Neurologia, Dipartimento di Neuroscienze e Riabilitazione, Azienda Ospedaliero-Universitaria, Arcispedale S. Anna, Ferrara

Background Perihematomal area an early decrease in cerebral blood flow (CBF) is a common finding in perihematomal area evidence for perihematomal ischemic penumbra remains controversial the fate of perihemorrhagic edematous tissue is still unknown

Purpose Computed Tomography Perfusion (CTP): CBF CBV MTT Computed Tomography Perfusion (CTP): seems to be able to discriminate between ischemic penumbra and infarcted tissue could represent a promising tool for the detection and the interpretation of time course of perfusion abnormalities associated with hematomas

Patients Fifty-five patients (25 male and 30 female; mean age ± SD = 68.7 ± 11.8 years; NIHSS at admission ± SD = 13.3 ± 5.3): diagnosis of acute supratentorial spontaneous intracerebral hemorrhage (SICH), proven by admission CT scan performed within 24 hours of onset (range = 1.3 - 22.3 hours) no infratentorial hematoma, secondary hemorrhage (tumor, trauma, coagulopathy, aneurysms and vascular malformation), hemorrhagic transformation of brain infarction, intraventricular hemorrhage, surgical hematoma evacuation, age lower than 20 years

Location and volumes Hematoma location was lobar in 23 patients and within basal ganglia in the remaining 32 patients Hematoma and perihematomal edema volumes were calculated using the formula AxBxC/2: (perihematomal edema volume = hematoma volume + perihematomal low density area volume – hematoma volume)

CTP studies CTP studies were performed by using a single-section CT scanner (CT Hispeed ZX/i; GE Medical System, Waukesha, Wis): a series of 45 CT scans acquired in a single slice (10-mm slice thickness, 80 kVp; 200 mAs; matrix 512 x 512; FOV 25-cm; total scan time 50 sec) during the automatic injection of 50 ml of non-ionic contrast agent at the rate of 3.5 ml/sec, starting 5 seconds before the initial image the single slice was located at hematoma level containing the largest volume of blood

CTP maps CBF CBV MTT Perfusion maps were generated for each patient (CT Perfusion 3 and 4, GE Medical System, Waukesha, Wis) with: a deconvolution-based algorithm (CBF = ml/100g/min; CBV = ml/100g; MTT = sec) large blood vessels were automatically excluded by the calculation

CTP mapping (3) (1) (2) (4) Four different region of interest (ROIs) were manually drawn on the baseline diagnostic CT scan: 1) the hemorrhagic core 2) the perihematomal low density area 3) a perilesional area of normal appearing brain tissue = 1 cm 4) a mirror area placed in the contralateral hemisphere

CTP measurements CBF CBV MTT Regional absolute levels of CBF (rCBF), CBV (rCBV), and MTT (rMTT) in both injured and apparently normal tissue rCBF levels < 10 ml/100g/min = ischemic; 10 - 20 ml/100g/min = penumbral; 20 - 40 ml/100g/min = oligemic and > 55 ml/100g/min = hyperperfusional rCBV levels lower and greater than 2.5 ml/100g = low and normal or high rMTT levels greater and lower than 5 seconds = high and normal or low

Study design NECT CBF CBV MTT CTP studies were scheduled within 24 hours, 48 hours, 5 days and 7 days after bleeding NIHSS, hematoma and perihematomal edema volumes were measured in the same time points

Statistics .....? After checking data for normality (Kolmogorov-Smirnov test): ANOVA and repeated measures ANOVA followed by Scheffè test, as post-hoc analysis Linear regression analysis A value of p < 0.05 was considered as statistically significant

CTP values distribution rCBF, rCBV and rMTT levels were concentrically distributed and gradually improve from the core to the periphery (ANOVA; p < 0.0001) at 24 and 48 hours

CTP values distribution The same distribution was observed for rCBF, rCBV and rMTT values at 5 and 7 days (ANOVA; p < 0.0001)

CTP values timing Compared to 24 hours: rCBF and rCBV levels increased and rMTT levels decreased at 48 hours; CTP parameters returned toward initial values at 5 days; rCBF and rCBV levels declined and rMTT levels were prolonged at 7 days in core and perihematomal area (ANOVA Repeated Measures; p < 0.0001)

CTP values timing rCBF, rCBV and rMTT levels demonstrated an identical time course in perilesional and contralateral normal appearing areas (ANOVA Repeated Measures; p < 0.0001)

Perihematomal absolute rCBF values Perihematomal absolute rCBF values were oligemic at 24 hours, were normal at 48 hours and became oligemic again at 5 and 7 days

Perihematomal rCBF patterns Perihematomal rCBF ischemic values were more frequent at 7 days than at 24 hours and were detected in 40% of patients at 7 days

Correlations Perihematomal rCBF and rCBV levels were inversely correlated with hematoma and edema volumes at 24 and 48 hours

Correlations Perihematomal rCBF and rCBV levels were inversely correlated only with edema volume at 5 and 7 days No association between CTP parameters and NIHSS in each time points

Limitations the ability of CTP in measuring absolute perfusion values is not widely accepted due to unresolved technical problems the potential perihematomal BBB breakdown was not corrected (possible overestimation of CTP values) no correlation with clinical outcome (mRS) at 3 months and hematoma enlargement limited coverage radiation exposure (low with a single slice protocol) contrast material administration (generally safe) NECT CBF CBV MTT

Discussion In the transition from acute to subacute phases, SICH is characterized by: a centrifugal gradient with an improvement from the core to the periphery which persists over time in each ROI evaluated a three-phasic perfusion pattern within and around the lesion and in the contralateral hemisphere indicating a global perfusion response to SICH At 7 days after bleeding: - perihematomal CBF values were oligemic probably in relation to edema formation - perihematomal ischemic CBF levels increased suggesting that an irreversible damage could occur in a subset of patients NECT CBF CBV MTT

Conclusions CTP has the potential: NECT CBF CBV MTT CTP has the potential: - to evaluate perfusion changes associated with the temporal evolution of SICH - to better understand the fate of perihematomal tissue