- Email: [email protected]
3D pseudocontinuous arterial spin-labeling perfusion imaging detected crossed cerebellar diaschisis in acute, subacute and chronic intracerebral hemorrhage
Clinical Imaging 50 (2018) 37–42
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: www.elsevier.com/locate/clinimag
3D pseudocontinuous arterial spin-labeling perfusion imaging detected crossed cerebellar diaschisis in acute, subacute and chronic intracerebral hemorrhage
T
⁎
Liang Yina, Shuangjuan Chenga, Jiangxi Xiaoa, , Ying Zhua, Shanshan Bua, Xiaodong Zhanga, Ran Liub, Yining Huangb, Sheng Xiec a b c
Department of Radiology, Peking University First Hospital, Beijing, China Department of Neurology, Peking University First Hospital, Beijing, China Department of Radiology, China-Japanese Friendship Hospital, Beijing, China.
A R T I C L E I N F O
A B S T R A C T
Keywords: Intracerebral hemorrhage Crossed cerebellar diaschisis Arterial spin-labeling
Objective: We aimed to evaluate the value of 3D pseudocontinuous arterial spin-labeling (pCASL) perfusion imaging detected crossed cerebellar diaschisis (CCD) at different stages of intracerebral hemorrhage (ICH). Materials and methods: We assessed bilateral cerebral blood flow (CBF) values of different brain regions and the relationships between the CCD and clinical status of 16 ICH patients. Results: The ICH patients had significantly lower CBF values in the contralateral cerebellum in acute, subacute and chronic stages. The subacute CCD had a significant correlation with clinical status. Conclusions: 3D pCASL may be an ideal tool to study the phenomenon and clinical consequences of ICH with CCD.
1. Introduction Crossed cerebellar diaschisis (CCD) is a phenomenon involving decreased cerebellar perfusion and glucose metabolism in the cerebellar hemisphere contralateral to a supratentorial cerebral lesion [1,2]. Although mostly seen with cerebral infarcts, CCD has been reported in other clinical conditions such as intracerebral hemorrhage, status epilepticus, tumors and encephalitis [3–7]. Animal studies have suggested that CCD is explained by the deactivation of cerebellar neurons caused by a reduction in excitatory impulses via the cortico-ponto-cerebellar tract [8,9]. Recent findings have suggested that CCD is not only a neuroradiological phenomenon, but also an important prognostic indicator of stroke recovery and treatment response [10,11]. In the last few decades, imaging studies including those using single photon emission computed tomography (SPECT) [4], positron emission tomography (PET) [12] and computed tomography (CT) perfusion imaging [13], have demonstrated CCD in patients with intracerebral hemorrhage (ICH). Most of these techniques are used as reference methods for perfusion imaging, but are they are not available in routine clinical care. The serial changes in cerebellar hypoperfusion and the prognostic value of CCD are still unclear. Thus, it is necessary to find an easy, noninvasive, and widely available imaging method for the detection
⁎
and intensive study of CCD. Arterial spin-labeling (ASL) is a novel noninvasive MRI method that uses arterial water as an endogenous tracer for perfusion imaging. Thus, it can be performed without the administration of contrast media or exposure to radiation, allowing reliable and repeatable cerebral blood flow (CBF) measurements in a wide spectrum of pathologic conditions [14]. Previous research has shown that the ASL technique, incorporating pseudocontinuous labeling with volumetric fast spin-echo and spiral readout can improved SNR and whole-brain coverage [15]. The purpose of this study was to evaluate the value of 3D pCASL in the detection of CCD at different stages of ICH and to identify the relevant imaging or clinical factors of CCD development. 2. Material and methods 2.1. Patient population This prospective study was approved by the local institutional review board, and written informed consent was obtained from all the patients. Sixteen patients with spontaneous ICH, who were hospitalized between May 2014 and April 2015, were screened and enrolled in this pilot study. The inclusion criteria for this study were as follows: (1)
Corresponding author at: Department of Radiology, Peking University First Hospital, Number 8, Xishiku Street, Xicheng District, Beijing 100034, China. E-mail address: [email protected] (J. Xiao).
https://doi.org/10.1016/j.clinimag.2017.12.007 Received 20 September 2017; Received in revised form 7 December 2017; Accepted 11 December 2017 0899-7071/ © 2017 Elsevier Inc. All rights reserved.
Clinical Imaging 50 (2018) 37–42
L. Yin et al.
Fig. 1. Patient 3. Quantitative analysis of the ASL images in a patient with right basal ganglia hemorrhage. (A, B) Three ROIs were drawn separately for the GM and WM of the frontal lobes. The ipsilateral CBF values for the frontal GM and WM were significantly reduced. (C, D) ROIs were manually traced to cover the 1-cm marginal radius around the hematoma and one side of cerebellum and then were mirrored to the respective contralateral side. The CBF values of the ipsilateral perihematoma and of the contralateral cerebellum were significantly reduced.
2.3. Image acquisition
age > 18 years old; (2) hematoma lesions localized unilaterally in the cerebral hemisphere diagnosed by CT; (3) hematoma volume < 30 ml; and (4) good imaging quality of the ASL study without motion artifacts. The exclusion criteria were as follows: (1) emergency surgical hematoma evacuation; (2) cerebral infarction or chronic cerebrovascular stenoocclusive disease; (3) hemorrhage related to trauma, tumor or vascular malformation; and (4) absent clinical history information. A total of 41 MRI scans were obtained from the 16 patients, who were scanned at the acute (9 scans), subacute (16 scans) and chronic (16 scans) stage. The clinical age of the ICH was based on the period between the MR imaging examination and the start of bleeding, which was considered to have occurred on the day of the onset of symptoms. According to the classification from the literature [16,17], we divided the ICH into an acute group (age, ≤ 3 days), a subacute group (age, approximately 2 weeks), and a chronic group (age, ≥ 1 month). The CBF was measured during each stage, although not all patients participated in the ASL study during every stage.
All the patients underwent non-enhanced computed tomography (CT) on a 64-slice CT scanner (Light speed VCT Xte, GE Healthcare, Milwaukee, WI, USA) with a 0.5-mm section thickness (120 kvp; 280 mA/slice) and a 240-mm FOV through the whole brain (24 slices; 512 × 512 matrix). Magnetic resonance acquisition was performed on a 3.0-T magnetic resonance scanner (GE Discovery 750, GE Healthcare, Milwaukee, WI, USA) using a standard 8-channel phase array head coil. The following conventional MRI sequences were included: spin-echo T1-weighted imaging (T1WI), fast spin-echo T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), 3D time of flight (TOF) magnetic resonance angiography (MRA), and fluid attenuated inversion recovery imaging (FLAIR). A 3D spiral fast spin echo (FSE) sequence was used to obtain the 3D pseudocontinuous ASL perfusion images. The scan parameters were as follows: post labeling delay, 2025 ms; spatial resolution, 3.64 mm; TR, 4844 ms; TE, 10.5 ms; FOV, 240 × 240 mm; matrix, 128 × 128; NEX, 3; bandwidth, ± 62.5 KHz; slice thickness, 4 mm; intersection gap, 0 mm; sections, 30; field number of slices, 36; acquisition time, 4 min 15 s.
2.2. NIHSS score and mRS score The National Institute of Health Stroke Scale (NIHSS) [18] was used to evaluate the neurological and functional statuses of the patients, as assessed by two experienced neurosurgeons at admission and 14 days after symptom onset. The Modified Rankin Scale (mRS) [19] score was estimated by the same neurosurgeons at 3 months after the ICH and was defined as the patient outcome.
2.4. Image analysis All the imaging data were transferred to an imaging workstation (Advantage Windows 4.6; GE Medical System, Milwaukee, WI, USA). The hematoma volume was calculated from the CT imaging using the formula (A × B × C) / 2, where A, B and C represent the dimensions of 38
Clinical Imaging 50 (2018) 37–42
L. Yin et al.
women ratio was 12:4. The mean time interval between symptom onset and the pCASL scans in the acute, subacute and chronic stages was 1.3 ± 0.5 (range, 1–2) days, 12.8 ± 1.4 (range, 10–14) days, and 42.6 ± 15.2 (range, 30–92) days, respectively. The mean mRS scores of the patients were 1.68 ± 0.4 (range, 1–3). The mean NIHSS scores of the patients at admission and at 14 days were 4.8 ± 5.3 (range, 1–9) and 2.9 ± 1.4 (range, 1–6), respectively. The hematomas were located in the basal ganglia in 11 patients, the thalamus in 2 patients, the frontal lobe in 1 patient, the parietal lobe in 1 patient and the temporal lobe in 1 patient. The clinical symptom initially demonstrated was limb weakness in 12 patients and both limb weakness and dysphasia in 4 patients.
the CT hyperdensity in the three axes perpendicular to each other [20]. The CBF values were measured in consensus by two experienced neuroradiologists, who were blinded to the clinical outcomes. The CBF maps were generated from a GE ADW4.6 workstation supplied with a dedicated software package (Functool; GE Medical System, Milwaukee, WI, USA). Three circular regions of interest (ROI) with areas of 80–100 mm2 were drawn separately for both the gray matter (GM) and white matter (WM) of the frontal lobes, parietal lobes, temporal lobes and occipital lobes, and then, the mean values of the three ROIs in the different cerebral areas were calculated, respectively. Other ROIs were manually traced to cover one side of the cerebellum and the 1-cm marginal radius around the hematoma, which was then mirrored to the contralateral side (Fig. 1). After the ROIs were drawn, the major blood vessels, ventricles and any other extra structures were excluded from the ROIs as much as possible, and then, the CBF was measured within each ROI. The degree of the cerebral CBF reduction was expressed as the asymmetry index of the cerebrum (AICR): [(CBFcontralateral − CBFipsilateral) / CBFcontralateral] × 100%. The degree of CCD severity was expressed as the asymmetry index of the cerebellum (AICL): [(CBFipsilateral − CBFcontralateral) / CBFipsilateral] × 100%.
3.2. Radiological features The mean hematoma volume of the patients was 15.1 ± 8.4 (range, 2.48–29.10) ml. Table 2 shows the regional lateralities of the CBF values. The ICH patients had significantly low CBF values in the contralateral cerebellum in the acute, subacute and chronic stages (P = 0.010, P = 0.014, P = 0.024, respectively). There were also low CBF values observed in the ipsilateral frontal GM (acute and chronic stage), frontal WM (subacute stage), parietal GM (chronic stage), temporal GM (subacute and chronic stage) and temporal WM (subacute stage). The CBF values of the ipsilateral perihematoma were significantly lower than those of the contralateral mirror area in the acute, subacute and chronic stages (P = 0.045, P < 0.001, P = 0.015, respectively) (Fig. 2). Table 3 shows the results concerning the relationships between the degree of CCD severity (AICL) and the degree of the cerebral perfusion abnormality (AICR), hematoma volume, NIHSS score and mRS score. In the acute stage, no significant correlations were found between the AICL and the AICR, hematoma volume, NIHSS score, or the mRS score. The AICL in the subacute stage had significant positive correlations with the hematoma volume (r = 0.531, P = 0.034), the NIHSS score at 14 days (r = 0.614, P = 0.011) and the AICR in the frontal GM (r = 0.531, P = 0.034), temporal GM (r = 0.748, P = 0.001), and the occipital GM (r = 0.530, P = 0.035). The AICL in the chronic stage had significant positive correlations with the hematoma volume (r = 0.638, P = 0.008) and the AICR in parietal GM (r = 0.560, P = 0.024), parietal WM (r = 0.656, P = 0.006), temporal GM (r = 0.663, P = 0.007), and the occipital GM (r = 0.575, P = 0.002). All the AICL and AICR values among the acute, subacute and chronic stages had no significant differences (P > 0.05). Fig. 3 shows a representative case of ICH at the different stages.
2.5. Statistical analysis Statistical analysis was performed with the commercially available software package SPSS 20.0 (IBM, Armonk, New York). The normality of each variable was assessed using the Kolmogorov–Smirnov test. The hematoma volumes, NIHSS scores, mRS scores and CBF values were summarized as the mean ± standard deviation. A paired t-test was used to determine the detection ability of the ipsilateral cerebral diaschisis and the crossed cerebellar diaschisis. The relationships between the degree of CCD severity (AICL) and the variables were assessed with Pearson's correlation test (AICR, hematoma volume) and Spearman's correlation test (NIHSS, mRS). The differences in the AICL and AICR among the acute, subacute and chronic stages were determined with one-way analysis of variance (ANOVA). All statistics were performed with a 0.05 level of significance. 3. Results 3.1. Demographic and clinical characteristics The following demographic and clinical characteristics of the study cohort are summarized in Table 1. The mean age of participants in the present study was 55.3 ± 10.0 (range, 37–71) years, and the men/ Table 1 Clinical and MRI characteristics of the study cohort Patient
Gender
Age (years)
ICH volume (ml)
Time to ASL (day)
Lesion side
NIHSS1 score
NIHSS2 score
mRS score
Clinical symptom
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
M M M F M M M M M M M M M F F F
44 51 37 60 54 43 74 55 50 57 50 52 71 62 58 66
20.08 8.18 21.90 21.02 23.60 12.70 6.28 23.67 20.10 2.48 29.10 20.20 13.70 2.98 6.43 8.67
1/14/31 1/14/51 1/13/41 1/12/36 1/11/45 1/14/34 2/11/31 2/11/32 2/14/44 14/36 13/92 10/37 13/53 13/38 14/30 14/51
L-BG L-BG R-BG R-BG R-BG L-BG L-BG R-FL R-TL L-BG R-BG R-BG R-BG R-TH L-TH L-PL
5 4 6 8 6 1 4 6 1 3 9 4 6 5 7 2
3 2 3 5 3 1 3 1 1 2 6 2 3 2 5 2
2 2 1 1 2 1 2 2 1 1 3 1 2 2 2 2
LW LW LW LW LW LW LW LW + LW LW LW + LW LW LW + LW + LW
dysphasia
dysphasia
dysphasia dysphasia
Note: R = right, L = left, BG = basal ganglia, FL = frontal lobe, PL = parietal lobe, TL = temporal lobe, TH = thalamus, LW = limb weakness, ICH = intracerebral hemorrhage, NIHSS1 = NIHSS at admission, NIHSS2 = NIHSS at 14 days.
39
Clinical Imaging 50 (2018) 37–42
L. Yin et al.
Table 2 Ipsilateral and contralateral CBF values in the different brain regions of the acute, subacute and chronic ICH. Acute stage
Cerebellum Frontal GM Frontal WM Parietal GM Parietal WM Temporal GM Temporal WM Occipital GM Occipital WM Perihematoma
P value
Ipsilateral
Contralateral
35.7 48.5 21.2 39.8 20.7 46.1 27.2 38.9 18.1 33.9
32.0 53.6 23.3 43.5 22.7 48.6 28.0 41.8 19.7 39.8
± ± ± ± ± ± ± ± ± ±
12.3 15.5 6.7 17.4 9.2 12.9 9.3 19.1 8.3 7.7
± ± ± ± ± ± ± ± ± ±
10.2 16.8 8.5 19.7 10.4 14.7 7.4 20.5 9.3 9.3
0.010⁎ 0.042⁎ 0.117 0.118 0.262 0.240 0.758 0.082 0.124 0.045⁎
Subacute stage
P value
Ipsilateral
Contralateral
31.1 46.9 19.9 34.9 16.7 41.4 21.1 32.6 15.5 26.7
28.9 50.0 22.4 38.3 17.4 46.6 24.1 35.0 16.1 37.0
± ± ± ± ± ± ± ± ± ±
8.4 11.3 4.7 11.6 5.5 10.0 6.8 11.9 6.3 6.0
± ± ± ± ± ± ± ± ± ±
7.6 10.6 6.5 14.1 5.5 10.7 8.2 12.7 6.6 6.7
0.014⁎ 0.081 0.010⁎ 0.161 0.451 < 0.001⁎ 0.009⁎ 0.061 0.385 < 0.001⁎
Chronic stage
P value
Ipsilateral
Contralateral
38.9 54.4 20.9 43.0 18.3 48.4 23.4 40.9 17.8 33.7
35.9 60.2 22.6 48.5 20.4 53.9 26.0 44.8 18.7 42.0
± ± ± ± ± ± ± ± ± ±
11.1 10.7 3.7 11.0 4.4 10.0 5.6 11.6 4.8 4.8
± ± ± ± ± ± ± ± ± ±
8.5 8.2 4.2 12.0 5.9 7.4 5.3 11.4 5.3 7.1
0.024⁎ 0.012⁎ 0.145 0.022⁎ 0.109 0.015⁎ 0.059 0.058 0.143 < 0.001⁎
Note: GM = gray matter, WM = white matter. Values are represented as the mean ± SD (ml/100 g/min). ⁎ P < 0.05.
4. Discussion
Table 3 Relationship between the degree of the CCD severity (AICL) and the degree of the cerebral perfusion abnormality (AICR), hematoma volume, NIHSS score and the mRS score in the acute, subacute and chronic stages.
The hypoperfusion and hypometabolism in the contralateral cerebellum in response to CCD has traditionally been detected by PET or SPECT. However, ASL offers the advantages of improved spatial resolution that allows longitudinal follow-up studies and the lack of concerns related to ionizing radiation exposure. Recently, studies have reported that the ASL method was able to detect CCD in hyperacute [21] and subacute [22] ischemic stroke patients. In addition, a validation study showed that ASL could be used as a noninvasive alternative to SPECT for evaluating CCD [23]. To our knowledge, only one publication has applied the ASL technique to diagnose CCD in cerebral hemorrhage patients [24]. Little is known about the serial changes in cerebellar hypoperfusion or the prognostic value of CCD. In this study, we detected CCD in patients with unilateral supratentorial ICH at different stages. The patients had significantly low CBF values in the contralateral cerebellum and the ipsilateral cerebrum in the acute, subacute and chronic stages, suggesting that 3D pCASL might be able to delineate CCD and ipsilateral cerebral diaschisis [24]. Our results might support those of earlier studies that demonstrated low regional cerebral perfusion in the ipsilateral hemisphere due to reduced metabolism because our analyses revealed low CBF values in some of the ipsilateral cerebral regions [24,25]. In addition, the CCD severity had no significant changes among the acute, subacute and chronic stage. Takasawa M et al. [26] reported that the mean AI in the cerebellum did not significantly change from the acute stage (16 ± 10 h) to the subacute stage (10 ± 5 days) in supratentorial infarct patients. Infeld et al. [27] found no statistically significant changes in cerebellar hypoperfusion between the acute stage (within 36 h after onset) and the chronic stage (6.5 ± 4 months) in infarct patients. Thus, our findings are consistent with those of previous studies.
AICR Frontal GM Frontal WM Parietal GM Parietal WM Temporal GM Temporal WM Occipital GM Occipital WM Perihematoma Hematoma volume NIHSS1 score NIHSS2 score mRS score
AICL (acute stage)
AICL (subacute stage)
AICL (chronic stage)
− 0.079 (0.841) 0.182 (0.639) 0.671 (0.048⁎) 0.048 (0.902) 0.649 (0.082) 0.209 (0.620) 0.512 (0.158) 0.340 (0.371) 0.521 (0.150) 0.053 (0.892) − 0.159 (0.683) – 0.478 (0.193)
0.531 (0.034⁎) 0.311 (0.241) − 0.005 (0.984) 0.477 (0.062) 0.748 (0.001⁎) 0.126 (0.655) 0.530 (0.035⁎) 0.376 (0.151) 0.192 (0.475) 0.531 (0.034⁎) – 0.614 (0.011⁎) 0.515 (0.041⁎)
0.373 0.276 0.560 0.656 0.663 0.398 0.575 0.386 0.621 0.638 – – 0.351
(0.154) (0.300) (0.024⁎) (0.006⁎) (0.007⁎) (0.142) (0.020⁎) (0.139) (0.014⁎) (0.008⁎)
(0.182)
Note: AICL = CBF asymmetry index of the cerebellum, AICR = CBF asymmetry index of the cerebrum, GM = gray matter, WM = white matter, NIHSS1 = NIHSS at admission, NIHSS2 = NIHSS at 14 days. ⁎ P < 0.05.
There is still debate in the literature regarding the correlation between the severity of CCD and the size of a supratentorial lesion. Previous research [28] has shown that CCD is closely related to the infarct volume and to the volume of the supratentorial hypoperfusion. However, a recent study [13] concluded that the hematoma volumes were not correlated with the degree of the CCD and that these volumes did not vary between the CCD-positive and CCD-negative patients. Different time-stages, imaging techniques and analysis methods may be
Fig. 2. Comparisons of the ipsilateral and contralateral CBF values in the different brain regions of the acute, subacute and chronic ICH. GM: gray matter, WM: white matter. *P < 0.05.
40
Clinical Imaging 50 (2018) 37–42
L. Yin et al.
Fig. 3. Patient 3. A 37-year-old man presented with dizziness and left limb weakness lasting for 1 day. (A) Noncontrast CT showing a right intracerebral hemorrhage in the basal ganglia. (B, C) MRA showing the normal cerebral vessels and vertebrobasilar system. (D) CBF maps at 1 day after ICH showing marked hypoperfusion in the ipsilateral cerebrum and a slight decrease in the CBF value in the contralateral cerebeum (AI = 5.6%). (E, F) CBF maps at 13 days and 41 days after ICH showing marked hypoperfusion in the ipsilateral cerebrum and the contralateral cerebellum (AI = 18.5%, AI = 19.2%, respectively).
(subacute and chronic stage) and occipital GM (subacute and chronic stage) are all statistically significant and have a positive linear correlation. This finding suggests that the degree of the supratentorial hypoperfusion is related to the CCD severity and that it can be observed with 3D pCASL imaging. A reported CT perfusion study of acute stroke revealed a similar significant correlation between the supratentorial hypoperfusion and the CCD severity [32]. The number of functionally impaired neurons and the resulting interruption of the cortico-pontocerebellar pathway maybe the main reason for such a correlation. Our study was limited by the small size of the patient group (16 patients). For a meaningful conclusion, a further study with a larger patient series is needed. Second, the CBF values, as measured by 3D pCASL, might vary according to variations in the labeling delays. This factor is important to know when considering the use of this technique for longitudinal follow-up. Third, SPECT or PET data were not acquired. Future studies combining 3D pCASL and other imaging techniques will help probide further validation. Finally, the AI values used to define the CCD severity were based upon a ROI covering the cerebellum, and did not reflect measurements specific to known functional regions of the cerebellum such as the medial, intermediate, and lateral zones [30]. CCD presenting as abnormal perfusion in the cerebellum that is contralateral to acute, subacute and chronic cerebral hemorrhage can be revealed by 3D pCASL perfusion imaging. The CCD severity in the subacute stage in patients with a supratentorial hemorrhage was correlated with the neurologic severity and clinical outcome. Because ASL allows serial imaging without radiation exposure, this technique can
partly responsible for the different results. In the present study, the hematoma volumes were not correlated with acute CCD but did have a significant positive correlation with both the subacute and chronic CCD. A reasonable speculation is that CCD in the acute stage may still be in a pathophysiologically unsettled status, which can manifest itself as reversible damage and potential tissue recovery [29]. In the clinical literature, only a few studies have focused on the correlation between the clinical status of the patients and the quantitative value of the CCD. In this study, the subacute CCD was significantly correlated with the clinical neurological defect (NIHSS score) and the outcome (mRS score). These correlations mean that as the degree of cerebellar hypoperfusion in the subacute stage increases, the neurologic severity and clinical outcome worsens. Several studies with relatively small sample sizes have also reported correlations with the clinical severity scales for subacute [26,28,30] and chronic CCD [11,31]. For acute CCD, no correlations with clinical severity scales have been established so far [26,28,31]. Thus, our results are consistent with those of previous studies. In contrast, other reports have concluded that the clinical severity at baseline or at outcome was not reflected by the degree of the CCD [13,24]. The different results were probably due to the time stage and pathologic cerebral stroke discrepancies from the different research centers. Regarding the relations between the degree of the supratentorial hypoperfusion and the degree of the CCD, our results show that the AICL and the AICR in the ipsilateral frontal GM (subacute stage), parietal GM (acute and chronic stage), parietal WM (chronic stage), temporal GM 41
Clinical Imaging 50 (2018) 37–42
L. Yin et al.
facilitate a better understanding of the long-term impact of CCD on disease outcome.
[16] Allkemper T, Tombach B, Schwindt W, Kugel H, Schilling M, Debus O, et al. Acute and subacute intracerebral hemorrhages: comparison of MR imaging at 1.5 and 3.0 T—initial experience. Radiology 2004;232(3):874–81. [17] Parizel PM, Makkat S, Van Miert E, Van Goethem JW, van den Hauwe L, De Schepper AM. Intracranial hemorrhage: principles of CT and MRI interpretation. Eur Radiol 2001;11(9):1770–83. [18] Brott T, Adams Jr. HP, Olinger CP, Marler JR, Barsan WG, Biller J, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989;20(7):864–70. [19] Farrell B, Godwin J, Richards S, Warlow C. The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991;54(12):1044–54. [20] Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27(8):1304–5. [21] Kang KM, Sohn CH, Choi SH, Jung KH, Yoo RE, Yun TJ, et al. Detection of crossed cerebellar diaschisis in hyperacute ischemic stroke using arterial spin-labeled MR imaging. PLoS One 2017;12(3):e0173971. [22] Chen S, Guan M, Lian HJ, Ma LJ, Shang JK, He S, et al. Crossed cerebellar diaschisis detected by arterial spin-labeled perfusion magnetic resonance imaging in subacute ischemic stroke. J Stroke Cerebrovasc Dis 2014;23(9):2378–83. [23] Kang KM, Sohn CH, Kim BS, Kim YI, Choi SH, Yun TJ, et al. Correlation of asymmetry indices measured by arterial spin-labeling MR imaging and SPECT in patients with crossed cerebellar diaschisis. AJNR Am J Neuroradiol 2015;36(9):1662–8. [24] Noguchi T, Nishihara M, Egashira Y, Azama S, Hirai T, Kitano I, et al. Arterial spinlabeling MR imaging of cerebral hemorrhages. Neuroradiology 2015;57(11):1135–44. [25] Kidwell CS, Saver JL, Mattiello J, Warach S, Liebeskind DS, Starkman S, et al. Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage. Neurology 2001;57(9):1611–7. [26] Takasawa M, Watanabe M, Yamamoto S, Hoshi T, Sasaki T, Hashikawa K, et al. Prognostic value of subacute crossed cerebellar diaschisis: single-photon emission CT study in patients with middle cerebral artery territory infarct. AJNR Am J Neuroradiol 2002;23(2):189–93. [27] Infeld B, Davis SM, Lichtenstein M, Mitchell PJ, Hopper JL. Crossed cerebellar diaschisis and brain recovery after stroke. Stroke 1995;26(1):90–5. [28] Sobesky J, Thiel A, Ghaemi M, Hilker RH, Rudolf J, Jacobs AH, et al. Crossed cerebellar diaschisis in acute human stroke: a PET study of serial changes and response to supratentorial reperfusion. J Cereb Blood Flow Metab 2005;25(12):1685–91. [29] Reivich M. Crossed cerebellar diaschisis. AJNR Am J Neuroradiol 1992;13(1):62–4. [30] Liu Y, Karonen JO, Nuutinen J, Vanninen E, Kuikka JT, Vanninen RL. Crossed cerebellar diaschisis in acute ischemic stroke: a study with serial SPECT and MRI. J Cereb Blood Flow Metab 2007;27(10):1724–32. [31] Serrati C, Marchal G, Rioux P, Viader F, Petit-Taboue MC, Lochon P, et al. Contralateral cerebellar hypometabolism: a predictor for stroke outcome? J Neurol Neurosurg Psychiatry 1994;57(2):174–9. [32] Jeon YW, Kim SH, Lee JY, Whang K, Kim MS, Kim YJ, et al. Dynamic CT perfusion imaging for the detection of crossed cerebellar diaschisis in acute ischemic stroke. Korean J Radiol 2012;13(1):12–9.
Acknowledgments and disclosure This work was supported by Peking University (BMU20140472). The authors report no conflicts of interest. References [1] Baron JC, Bousser MG, Comar D, Castaigne P. “Crossed cerebellar diaschisis” in human supratentorial brain infarction. Trans Am Neurol Assoc 1981;105:459–61. [2] Yamauchi H, Fukuyama H, Kimura J. Hemodynamic and metabolic changes in crossed cerebellar hypoperfusion. Stroke 1992;23(6):855–60. [3] Kunz WG, Sommer WH, Hohne C, Fabritius MP, Schuler F, Dorn F, et al. Crossed cerebellar diaschisis in acute ischemic stroke: impact on morphologic and functional outcome. J Cereb Blood Flow Metab 2017;37(11):3615–24. (271678X16686594). [4] Lim JS, Ryu YH, Kim BM, Lee JD. Crossed cerebellar diaschisis due to intracranial hematoma in basal ganglia or thalamus. J Nucl Med 1998;39(12):2044–7. [5] Bailly P, Bazire A, Prat G, Ben Salem D. Crossed cerebellar diaschisis in status epilepticus. Presse Med 2017;46(1):117–8. [6] Calabria F, Schillaci O. Recurrent glioma and crossed cerebellar diaschisis in a patient examined with 18F-DOPA and 18F-FDG PET/CT. Clin Nucl Med 2012;37(9):878–9. [7] Mahale R, Mehta A, Rangasetty S. Crossed cerebellar diaschisis due to Rasmussen encephalitis. Pediatr Neurol 2015;53(3):272–3. [8] Gold L, Lauritzen M. Neuronal deactivation explains decreased cerebellar blood flow in response to focal cerebral ischemia or suppressed neocortical function. Proc Natl Acad Sci U S A 2002;99(11):7699–704. [9] Dettmers C, Hartmann A, Rommel T, Hartmann S, Pappata S, Baron JC. Contralateral cerebellar diaschisis 7 hours after MCA-occlusion in primates. Neurol Res 1995;17(2):109–12. [10] Seitz RJ, Azari NP, Knorr U, Binkofski F, Herzog H, Freund HJ. The role of diaschisis in stroke recovery. Stroke 1999;30(9):1844–50. [11] Szilagyi G, Vas A, Kerenyi L, Nagy Z, Csiba L, Gulyas B. Correlation between crossed cerebellar diaschisis and clinical neurological scales. Acta Neurol Scand 2012;125(6):373–81. [12] Di Piero V, Chollet F, Dolan RJ, Thomas DJ, Frackowiak R. The functional nature of cerebellar diaschisis. Stroke 1990;21(9):1365–9. [13] Fu J, Chen WJ, Wu GY, Cheng JL, Wang MH, Zhuge Q, et al. Whole-brain 320detector row dynamic volume CT perfusion detected crossed cerebellar diaschisis after spontaneous intracerebral hemorrhage. Neuroradiology 2015;57(2):179–87. [14] Haller S, Zaharchuk G, Thomas DL, Lovblad KO, Barkhof F, Golay X. Arterial spin labeling perfusion of the brain: emerging clinical applications. Radiology 2016;281(2):337–56. [15] Dai W, Garcia D, de Bazelaire C, Alsop DC. Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magn Reson Med 2008;60(6):1488–97.
42
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: www.elsevier.com/locate/clinimag
3D pseudocontinuous arterial spin-labeling perfusion imaging detected crossed cerebellar diaschisis in acute, subacute and chronic intracerebral hemorrhage
T
⁎
Liang Yina, Shuangjuan Chenga, Jiangxi Xiaoa, , Ying Zhua, Shanshan Bua, Xiaodong Zhanga, Ran Liub, Yining Huangb, Sheng Xiec a b c
Department of Radiology, Peking University First Hospital, Beijing, China Department of Neurology, Peking University First Hospital, Beijing, China Department of Radiology, China-Japanese Friendship Hospital, Beijing, China.
A R T I C L E I N F O
A B S T R A C T
Keywords: Intracerebral hemorrhage Crossed cerebellar diaschisis Arterial spin-labeling
Objective: We aimed to evaluate the value of 3D pseudocontinuous arterial spin-labeling (pCASL) perfusion imaging detected crossed cerebellar diaschisis (CCD) at different stages of intracerebral hemorrhage (ICH). Materials and methods: We assessed bilateral cerebral blood flow (CBF) values of different brain regions and the relationships between the CCD and clinical status of 16 ICH patients. Results: The ICH patients had significantly lower CBF values in the contralateral cerebellum in acute, subacute and chronic stages. The subacute CCD had a significant correlation with clinical status. Conclusions: 3D pCASL may be an ideal tool to study the phenomenon and clinical consequences of ICH with CCD.
1. Introduction Crossed cerebellar diaschisis (CCD) is a phenomenon involving decreased cerebellar perfusion and glucose metabolism in the cerebellar hemisphere contralateral to a supratentorial cerebral lesion [1,2]. Although mostly seen with cerebral infarcts, CCD has been reported in other clinical conditions such as intracerebral hemorrhage, status epilepticus, tumors and encephalitis [3–7]. Animal studies have suggested that CCD is explained by the deactivation of cerebellar neurons caused by a reduction in excitatory impulses via the cortico-ponto-cerebellar tract [8,9]. Recent findings have suggested that CCD is not only a neuroradiological phenomenon, but also an important prognostic indicator of stroke recovery and treatment response [10,11]. In the last few decades, imaging studies including those using single photon emission computed tomography (SPECT) [4], positron emission tomography (PET) [12] and computed tomography (CT) perfusion imaging [13], have demonstrated CCD in patients with intracerebral hemorrhage (ICH). Most of these techniques are used as reference methods for perfusion imaging, but are they are not available in routine clinical care. The serial changes in cerebellar hypoperfusion and the prognostic value of CCD are still unclear. Thus, it is necessary to find an easy, noninvasive, and widely available imaging method for the detection
⁎
and intensive study of CCD. Arterial spin-labeling (ASL) is a novel noninvasive MRI method that uses arterial water as an endogenous tracer for perfusion imaging. Thus, it can be performed without the administration of contrast media or exposure to radiation, allowing reliable and repeatable cerebral blood flow (CBF) measurements in a wide spectrum of pathologic conditions [14]. Previous research has shown that the ASL technique, incorporating pseudocontinuous labeling with volumetric fast spin-echo and spiral readout can improved SNR and whole-brain coverage [15]. The purpose of this study was to evaluate the value of 3D pCASL in the detection of CCD at different stages of ICH and to identify the relevant imaging or clinical factors of CCD development. 2. Material and methods 2.1. Patient population This prospective study was approved by the local institutional review board, and written informed consent was obtained from all the patients. Sixteen patients with spontaneous ICH, who were hospitalized between May 2014 and April 2015, were screened and enrolled in this pilot study. The inclusion criteria for this study were as follows: (1)
Corresponding author at: Department of Radiology, Peking University First Hospital, Number 8, Xishiku Street, Xicheng District, Beijing 100034, China. E-mail address: [email protected] (J. Xiao).
https://doi.org/10.1016/j.clinimag.2017.12.007 Received 20 September 2017; Received in revised form 7 December 2017; Accepted 11 December 2017 0899-7071/ © 2017 Elsevier Inc. All rights reserved.
Clinical Imaging 50 (2018) 37–42
L. Yin et al.
Fig. 1. Patient 3. Quantitative analysis of the ASL images in a patient with right basal ganglia hemorrhage. (A, B) Three ROIs were drawn separately for the GM and WM of the frontal lobes. The ipsilateral CBF values for the frontal GM and WM were significantly reduced. (C, D) ROIs were manually traced to cover the 1-cm marginal radius around the hematoma and one side of cerebellum and then were mirrored to the respective contralateral side. The CBF values of the ipsilateral perihematoma and of the contralateral cerebellum were significantly reduced.
2.3. Image acquisition
age > 18 years old; (2) hematoma lesions localized unilaterally in the cerebral hemisphere diagnosed by CT; (3) hematoma volume < 30 ml; and (4) good imaging quality of the ASL study without motion artifacts. The exclusion criteria were as follows: (1) emergency surgical hematoma evacuation; (2) cerebral infarction or chronic cerebrovascular stenoocclusive disease; (3) hemorrhage related to trauma, tumor or vascular malformation; and (4) absent clinical history information. A total of 41 MRI scans were obtained from the 16 patients, who were scanned at the acute (9 scans), subacute (16 scans) and chronic (16 scans) stage. The clinical age of the ICH was based on the period between the MR imaging examination and the start of bleeding, which was considered to have occurred on the day of the onset of symptoms. According to the classification from the literature [16,17], we divided the ICH into an acute group (age, ≤ 3 days), a subacute group (age, approximately 2 weeks), and a chronic group (age, ≥ 1 month). The CBF was measured during each stage, although not all patients participated in the ASL study during every stage.
All the patients underwent non-enhanced computed tomography (CT) on a 64-slice CT scanner (Light speed VCT Xte, GE Healthcare, Milwaukee, WI, USA) with a 0.5-mm section thickness (120 kvp; 280 mA/slice) and a 240-mm FOV through the whole brain (24 slices; 512 × 512 matrix). Magnetic resonance acquisition was performed on a 3.0-T magnetic resonance scanner (GE Discovery 750, GE Healthcare, Milwaukee, WI, USA) using a standard 8-channel phase array head coil. The following conventional MRI sequences were included: spin-echo T1-weighted imaging (T1WI), fast spin-echo T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), 3D time of flight (TOF) magnetic resonance angiography (MRA), and fluid attenuated inversion recovery imaging (FLAIR). A 3D spiral fast spin echo (FSE) sequence was used to obtain the 3D pseudocontinuous ASL perfusion images. The scan parameters were as follows: post labeling delay, 2025 ms; spatial resolution, 3.64 mm; TR, 4844 ms; TE, 10.5 ms; FOV, 240 × 240 mm; matrix, 128 × 128; NEX, 3; bandwidth, ± 62.5 KHz; slice thickness, 4 mm; intersection gap, 0 mm; sections, 30; field number of slices, 36; acquisition time, 4 min 15 s.
2.2. NIHSS score and mRS score The National Institute of Health Stroke Scale (NIHSS) [18] was used to evaluate the neurological and functional statuses of the patients, as assessed by two experienced neurosurgeons at admission and 14 days after symptom onset. The Modified Rankin Scale (mRS) [19] score was estimated by the same neurosurgeons at 3 months after the ICH and was defined as the patient outcome.
2.4. Image analysis All the imaging data were transferred to an imaging workstation (Advantage Windows 4.6; GE Medical System, Milwaukee, WI, USA). The hematoma volume was calculated from the CT imaging using the formula (A × B × C) / 2, where A, B and C represent the dimensions of 38
Clinical Imaging 50 (2018) 37–42
L. Yin et al.
women ratio was 12:4. The mean time interval between symptom onset and the pCASL scans in the acute, subacute and chronic stages was 1.3 ± 0.5 (range, 1–2) days, 12.8 ± 1.4 (range, 10–14) days, and 42.6 ± 15.2 (range, 30–92) days, respectively. The mean mRS scores of the patients were 1.68 ± 0.4 (range, 1–3). The mean NIHSS scores of the patients at admission and at 14 days were 4.8 ± 5.3 (range, 1–9) and 2.9 ± 1.4 (range, 1–6), respectively. The hematomas were located in the basal ganglia in 11 patients, the thalamus in 2 patients, the frontal lobe in 1 patient, the parietal lobe in 1 patient and the temporal lobe in 1 patient. The clinical symptom initially demonstrated was limb weakness in 12 patients and both limb weakness and dysphasia in 4 patients.
the CT hyperdensity in the three axes perpendicular to each other [20]. The CBF values were measured in consensus by two experienced neuroradiologists, who were blinded to the clinical outcomes. The CBF maps were generated from a GE ADW4.6 workstation supplied with a dedicated software package (Functool; GE Medical System, Milwaukee, WI, USA). Three circular regions of interest (ROI) with areas of 80–100 mm2 were drawn separately for both the gray matter (GM) and white matter (WM) of the frontal lobes, parietal lobes, temporal lobes and occipital lobes, and then, the mean values of the three ROIs in the different cerebral areas were calculated, respectively. Other ROIs were manually traced to cover one side of the cerebellum and the 1-cm marginal radius around the hematoma, which was then mirrored to the contralateral side (Fig. 1). After the ROIs were drawn, the major blood vessels, ventricles and any other extra structures were excluded from the ROIs as much as possible, and then, the CBF was measured within each ROI. The degree of the cerebral CBF reduction was expressed as the asymmetry index of the cerebrum (AICR): [(CBFcontralateral − CBFipsilateral) / CBFcontralateral] × 100%. The degree of CCD severity was expressed as the asymmetry index of the cerebellum (AICL): [(CBFipsilateral − CBFcontralateral) / CBFipsilateral] × 100%.
3.2. Radiological features The mean hematoma volume of the patients was 15.1 ± 8.4 (range, 2.48–29.10) ml. Table 2 shows the regional lateralities of the CBF values. The ICH patients had significantly low CBF values in the contralateral cerebellum in the acute, subacute and chronic stages (P = 0.010, P = 0.014, P = 0.024, respectively). There were also low CBF values observed in the ipsilateral frontal GM (acute and chronic stage), frontal WM (subacute stage), parietal GM (chronic stage), temporal GM (subacute and chronic stage) and temporal WM (subacute stage). The CBF values of the ipsilateral perihematoma were significantly lower than those of the contralateral mirror area in the acute, subacute and chronic stages (P = 0.045, P < 0.001, P = 0.015, respectively) (Fig. 2). Table 3 shows the results concerning the relationships between the degree of CCD severity (AICL) and the degree of the cerebral perfusion abnormality (AICR), hematoma volume, NIHSS score and mRS score. In the acute stage, no significant correlations were found between the AICL and the AICR, hematoma volume, NIHSS score, or the mRS score. The AICL in the subacute stage had significant positive correlations with the hematoma volume (r = 0.531, P = 0.034), the NIHSS score at 14 days (r = 0.614, P = 0.011) and the AICR in the frontal GM (r = 0.531, P = 0.034), temporal GM (r = 0.748, P = 0.001), and the occipital GM (r = 0.530, P = 0.035). The AICL in the chronic stage had significant positive correlations with the hematoma volume (r = 0.638, P = 0.008) and the AICR in parietal GM (r = 0.560, P = 0.024), parietal WM (r = 0.656, P = 0.006), temporal GM (r = 0.663, P = 0.007), and the occipital GM (r = 0.575, P = 0.002). All the AICL and AICR values among the acute, subacute and chronic stages had no significant differences (P > 0.05). Fig. 3 shows a representative case of ICH at the different stages.
2.5. Statistical analysis Statistical analysis was performed with the commercially available software package SPSS 20.0 (IBM, Armonk, New York). The normality of each variable was assessed using the Kolmogorov–Smirnov test. The hematoma volumes, NIHSS scores, mRS scores and CBF values were summarized as the mean ± standard deviation. A paired t-test was used to determine the detection ability of the ipsilateral cerebral diaschisis and the crossed cerebellar diaschisis. The relationships between the degree of CCD severity (AICL) and the variables were assessed with Pearson's correlation test (AICR, hematoma volume) and Spearman's correlation test (NIHSS, mRS). The differences in the AICL and AICR among the acute, subacute and chronic stages were determined with one-way analysis of variance (ANOVA). All statistics were performed with a 0.05 level of significance. 3. Results 3.1. Demographic and clinical characteristics The following demographic and clinical characteristics of the study cohort are summarized in Table 1. The mean age of participants in the present study was 55.3 ± 10.0 (range, 37–71) years, and the men/ Table 1 Clinical and MRI characteristics of the study cohort Patient
Gender
Age (years)
ICH volume (ml)
Time to ASL (day)
Lesion side
NIHSS1 score
NIHSS2 score
mRS score
Clinical symptom
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
M M M F M M M M M M M M M F F F
44 51 37 60 54 43 74 55 50 57 50 52 71 62 58 66
20.08 8.18 21.90 21.02 23.60 12.70 6.28 23.67 20.10 2.48 29.10 20.20 13.70 2.98 6.43 8.67
1/14/31 1/14/51 1/13/41 1/12/36 1/11/45 1/14/34 2/11/31 2/11/32 2/14/44 14/36 13/92 10/37 13/53 13/38 14/30 14/51
L-BG L-BG R-BG R-BG R-BG L-BG L-BG R-FL R-TL L-BG R-BG R-BG R-BG R-TH L-TH L-PL
5 4 6 8 6 1 4 6 1 3 9 4 6 5 7 2
3 2 3 5 3 1 3 1 1 2 6 2 3 2 5 2
2 2 1 1 2 1 2 2 1 1 3 1 2 2 2 2
LW LW LW LW LW LW LW LW + LW LW LW + LW LW LW + LW + LW
dysphasia
dysphasia
dysphasia dysphasia
Note: R = right, L = left, BG = basal ganglia, FL = frontal lobe, PL = parietal lobe, TL = temporal lobe, TH = thalamus, LW = limb weakness, ICH = intracerebral hemorrhage, NIHSS1 = NIHSS at admission, NIHSS2 = NIHSS at 14 days.
39
Clinical Imaging 50 (2018) 37–42
L. Yin et al.
Table 2 Ipsilateral and contralateral CBF values in the different brain regions of the acute, subacute and chronic ICH. Acute stage
Cerebellum Frontal GM Frontal WM Parietal GM Parietal WM Temporal GM Temporal WM Occipital GM Occipital WM Perihematoma
P value
Ipsilateral
Contralateral
35.7 48.5 21.2 39.8 20.7 46.1 27.2 38.9 18.1 33.9
32.0 53.6 23.3 43.5 22.7 48.6 28.0 41.8 19.7 39.8
± ± ± ± ± ± ± ± ± ±
12.3 15.5 6.7 17.4 9.2 12.9 9.3 19.1 8.3 7.7
± ± ± ± ± ± ± ± ± ±
10.2 16.8 8.5 19.7 10.4 14.7 7.4 20.5 9.3 9.3
0.010⁎ 0.042⁎ 0.117 0.118 0.262 0.240 0.758 0.082 0.124 0.045⁎
Subacute stage
P value
Ipsilateral
Contralateral
31.1 46.9 19.9 34.9 16.7 41.4 21.1 32.6 15.5 26.7
28.9 50.0 22.4 38.3 17.4 46.6 24.1 35.0 16.1 37.0
± ± ± ± ± ± ± ± ± ±
8.4 11.3 4.7 11.6 5.5 10.0 6.8 11.9 6.3 6.0
± ± ± ± ± ± ± ± ± ±
7.6 10.6 6.5 14.1 5.5 10.7 8.2 12.7 6.6 6.7
0.014⁎ 0.081 0.010⁎ 0.161 0.451 < 0.001⁎ 0.009⁎ 0.061 0.385 < 0.001⁎
Chronic stage
P value
Ipsilateral
Contralateral
38.9 54.4 20.9 43.0 18.3 48.4 23.4 40.9 17.8 33.7
35.9 60.2 22.6 48.5 20.4 53.9 26.0 44.8 18.7 42.0
± ± ± ± ± ± ± ± ± ±
11.1 10.7 3.7 11.0 4.4 10.0 5.6 11.6 4.8 4.8
± ± ± ± ± ± ± ± ± ±
8.5 8.2 4.2 12.0 5.9 7.4 5.3 11.4 5.3 7.1
0.024⁎ 0.012⁎ 0.145 0.022⁎ 0.109 0.015⁎ 0.059 0.058 0.143 < 0.001⁎
Note: GM = gray matter, WM = white matter. Values are represented as the mean ± SD (ml/100 g/min). ⁎ P < 0.05.
4. Discussion
Table 3 Relationship between the degree of the CCD severity (AICL) and the degree of the cerebral perfusion abnormality (AICR), hematoma volume, NIHSS score and the mRS score in the acute, subacute and chronic stages.
The hypoperfusion and hypometabolism in the contralateral cerebellum in response to CCD has traditionally been detected by PET or SPECT. However, ASL offers the advantages of improved spatial resolution that allows longitudinal follow-up studies and the lack of concerns related to ionizing radiation exposure. Recently, studies have reported that the ASL method was able to detect CCD in hyperacute [21] and subacute [22] ischemic stroke patients. In addition, a validation study showed that ASL could be used as a noninvasive alternative to SPECT for evaluating CCD [23]. To our knowledge, only one publication has applied the ASL technique to diagnose CCD in cerebral hemorrhage patients [24]. Little is known about the serial changes in cerebellar hypoperfusion or the prognostic value of CCD. In this study, we detected CCD in patients with unilateral supratentorial ICH at different stages. The patients had significantly low CBF values in the contralateral cerebellum and the ipsilateral cerebrum in the acute, subacute and chronic stages, suggesting that 3D pCASL might be able to delineate CCD and ipsilateral cerebral diaschisis [24]. Our results might support those of earlier studies that demonstrated low regional cerebral perfusion in the ipsilateral hemisphere due to reduced metabolism because our analyses revealed low CBF values in some of the ipsilateral cerebral regions [24,25]. In addition, the CCD severity had no significant changes among the acute, subacute and chronic stage. Takasawa M et al. [26] reported that the mean AI in the cerebellum did not significantly change from the acute stage (16 ± 10 h) to the subacute stage (10 ± 5 days) in supratentorial infarct patients. Infeld et al. [27] found no statistically significant changes in cerebellar hypoperfusion between the acute stage (within 36 h after onset) and the chronic stage (6.5 ± 4 months) in infarct patients. Thus, our findings are consistent with those of previous studies.
AICR Frontal GM Frontal WM Parietal GM Parietal WM Temporal GM Temporal WM Occipital GM Occipital WM Perihematoma Hematoma volume NIHSS1 score NIHSS2 score mRS score
AICL (acute stage)
AICL (subacute stage)
AICL (chronic stage)
− 0.079 (0.841) 0.182 (0.639) 0.671 (0.048⁎) 0.048 (0.902) 0.649 (0.082) 0.209 (0.620) 0.512 (0.158) 0.340 (0.371) 0.521 (0.150) 0.053 (0.892) − 0.159 (0.683) – 0.478 (0.193)
0.531 (0.034⁎) 0.311 (0.241) − 0.005 (0.984) 0.477 (0.062) 0.748 (0.001⁎) 0.126 (0.655) 0.530 (0.035⁎) 0.376 (0.151) 0.192 (0.475) 0.531 (0.034⁎) – 0.614 (0.011⁎) 0.515 (0.041⁎)
0.373 0.276 0.560 0.656 0.663 0.398 0.575 0.386 0.621 0.638 – – 0.351
(0.154) (0.300) (0.024⁎) (0.006⁎) (0.007⁎) (0.142) (0.020⁎) (0.139) (0.014⁎) (0.008⁎)
(0.182)
Note: AICL = CBF asymmetry index of the cerebellum, AICR = CBF asymmetry index of the cerebrum, GM = gray matter, WM = white matter, NIHSS1 = NIHSS at admission, NIHSS2 = NIHSS at 14 days. ⁎ P < 0.05.
There is still debate in the literature regarding the correlation between the severity of CCD and the size of a supratentorial lesion. Previous research [28] has shown that CCD is closely related to the infarct volume and to the volume of the supratentorial hypoperfusion. However, a recent study [13] concluded that the hematoma volumes were not correlated with the degree of the CCD and that these volumes did not vary between the CCD-positive and CCD-negative patients. Different time-stages, imaging techniques and analysis methods may be
Fig. 2. Comparisons of the ipsilateral and contralateral CBF values in the different brain regions of the acute, subacute and chronic ICH. GM: gray matter, WM: white matter. *P < 0.05.
40
Clinical Imaging 50 (2018) 37–42
L. Yin et al.
Fig. 3. Patient 3. A 37-year-old man presented with dizziness and left limb weakness lasting for 1 day. (A) Noncontrast CT showing a right intracerebral hemorrhage in the basal ganglia. (B, C) MRA showing the normal cerebral vessels and vertebrobasilar system. (D) CBF maps at 1 day after ICH showing marked hypoperfusion in the ipsilateral cerebrum and a slight decrease in the CBF value in the contralateral cerebeum (AI = 5.6%). (E, F) CBF maps at 13 days and 41 days after ICH showing marked hypoperfusion in the ipsilateral cerebrum and the contralateral cerebellum (AI = 18.5%, AI = 19.2%, respectively).
(subacute and chronic stage) and occipital GM (subacute and chronic stage) are all statistically significant and have a positive linear correlation. This finding suggests that the degree of the supratentorial hypoperfusion is related to the CCD severity and that it can be observed with 3D pCASL imaging. A reported CT perfusion study of acute stroke revealed a similar significant correlation between the supratentorial hypoperfusion and the CCD severity [32]. The number of functionally impaired neurons and the resulting interruption of the cortico-pontocerebellar pathway maybe the main reason for such a correlation. Our study was limited by the small size of the patient group (16 patients). For a meaningful conclusion, a further study with a larger patient series is needed. Second, the CBF values, as measured by 3D pCASL, might vary according to variations in the labeling delays. This factor is important to know when considering the use of this technique for longitudinal follow-up. Third, SPECT or PET data were not acquired. Future studies combining 3D pCASL and other imaging techniques will help probide further validation. Finally, the AI values used to define the CCD severity were based upon a ROI covering the cerebellum, and did not reflect measurements specific to known functional regions of the cerebellum such as the medial, intermediate, and lateral zones [30]. CCD presenting as abnormal perfusion in the cerebellum that is contralateral to acute, subacute and chronic cerebral hemorrhage can be revealed by 3D pCASL perfusion imaging. The CCD severity in the subacute stage in patients with a supratentorial hemorrhage was correlated with the neurologic severity and clinical outcome. Because ASL allows serial imaging without radiation exposure, this technique can
partly responsible for the different results. In the present study, the hematoma volumes were not correlated with acute CCD but did have a significant positive correlation with both the subacute and chronic CCD. A reasonable speculation is that CCD in the acute stage may still be in a pathophysiologically unsettled status, which can manifest itself as reversible damage and potential tissue recovery [29]. In the clinical literature, only a few studies have focused on the correlation between the clinical status of the patients and the quantitative value of the CCD. In this study, the subacute CCD was significantly correlated with the clinical neurological defect (NIHSS score) and the outcome (mRS score). These correlations mean that as the degree of cerebellar hypoperfusion in the subacute stage increases, the neurologic severity and clinical outcome worsens. Several studies with relatively small sample sizes have also reported correlations with the clinical severity scales for subacute [26,28,30] and chronic CCD [11,31]. For acute CCD, no correlations with clinical severity scales have been established so far [26,28,31]. Thus, our results are consistent with those of previous studies. In contrast, other reports have concluded that the clinical severity at baseline or at outcome was not reflected by the degree of the CCD [13,24]. The different results were probably due to the time stage and pathologic cerebral stroke discrepancies from the different research centers. Regarding the relations between the degree of the supratentorial hypoperfusion and the degree of the CCD, our results show that the AICL and the AICR in the ipsilateral frontal GM (subacute stage), parietal GM (acute and chronic stage), parietal WM (chronic stage), temporal GM 41
Clinical Imaging 50 (2018) 37–42
L. Yin et al.
facilitate a better understanding of the long-term impact of CCD on disease outcome.
[16] Allkemper T, Tombach B, Schwindt W, Kugel H, Schilling M, Debus O, et al. Acute and subacute intracerebral hemorrhages: comparison of MR imaging at 1.5 and 3.0 T—initial experience. Radiology 2004;232(3):874–81. [17] Parizel PM, Makkat S, Van Miert E, Van Goethem JW, van den Hauwe L, De Schepper AM. Intracranial hemorrhage: principles of CT and MRI interpretation. Eur Radiol 2001;11(9):1770–83. [18] Brott T, Adams Jr. HP, Olinger CP, Marler JR, Barsan WG, Biller J, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989;20(7):864–70. [19] Farrell B, Godwin J, Richards S, Warlow C. The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991;54(12):1044–54. [20] Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27(8):1304–5. [21] Kang KM, Sohn CH, Choi SH, Jung KH, Yoo RE, Yun TJ, et al. Detection of crossed cerebellar diaschisis in hyperacute ischemic stroke using arterial spin-labeled MR imaging. PLoS One 2017;12(3):e0173971. [22] Chen S, Guan M, Lian HJ, Ma LJ, Shang JK, He S, et al. Crossed cerebellar diaschisis detected by arterial spin-labeled perfusion magnetic resonance imaging in subacute ischemic stroke. J Stroke Cerebrovasc Dis 2014;23(9):2378–83. [23] Kang KM, Sohn CH, Kim BS, Kim YI, Choi SH, Yun TJ, et al. Correlation of asymmetry indices measured by arterial spin-labeling MR imaging and SPECT in patients with crossed cerebellar diaschisis. AJNR Am J Neuroradiol 2015;36(9):1662–8. [24] Noguchi T, Nishihara M, Egashira Y, Azama S, Hirai T, Kitano I, et al. Arterial spinlabeling MR imaging of cerebral hemorrhages. Neuroradiology 2015;57(11):1135–44. [25] Kidwell CS, Saver JL, Mattiello J, Warach S, Liebeskind DS, Starkman S, et al. Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage. Neurology 2001;57(9):1611–7. [26] Takasawa M, Watanabe M, Yamamoto S, Hoshi T, Sasaki T, Hashikawa K, et al. Prognostic value of subacute crossed cerebellar diaschisis: single-photon emission CT study in patients with middle cerebral artery territory infarct. AJNR Am J Neuroradiol 2002;23(2):189–93. [27] Infeld B, Davis SM, Lichtenstein M, Mitchell PJ, Hopper JL. Crossed cerebellar diaschisis and brain recovery after stroke. Stroke 1995;26(1):90–5. [28] Sobesky J, Thiel A, Ghaemi M, Hilker RH, Rudolf J, Jacobs AH, et al. Crossed cerebellar diaschisis in acute human stroke: a PET study of serial changes and response to supratentorial reperfusion. J Cereb Blood Flow Metab 2005;25(12):1685–91. [29] Reivich M. Crossed cerebellar diaschisis. AJNR Am J Neuroradiol 1992;13(1):62–4. [30] Liu Y, Karonen JO, Nuutinen J, Vanninen E, Kuikka JT, Vanninen RL. Crossed cerebellar diaschisis in acute ischemic stroke: a study with serial SPECT and MRI. J Cereb Blood Flow Metab 2007;27(10):1724–32. [31] Serrati C, Marchal G, Rioux P, Viader F, Petit-Taboue MC, Lochon P, et al. Contralateral cerebellar hypometabolism: a predictor for stroke outcome? J Neurol Neurosurg Psychiatry 1994;57(2):174–9. [32] Jeon YW, Kim SH, Lee JY, Whang K, Kim MS, Kim YJ, et al. Dynamic CT perfusion imaging for the detection of crossed cerebellar diaschisis in acute ischemic stroke. Korean J Radiol 2012;13(1):12–9.
Acknowledgments and disclosure This work was supported by Peking University (BMU20140472). The authors report no conflicts of interest. References [1] Baron JC, Bousser MG, Comar D, Castaigne P. “Crossed cerebellar diaschisis” in human supratentorial brain infarction. Trans Am Neurol Assoc 1981;105:459–61. [2] Yamauchi H, Fukuyama H, Kimura J. Hemodynamic and metabolic changes in crossed cerebellar hypoperfusion. Stroke 1992;23(6):855–60. [3] Kunz WG, Sommer WH, Hohne C, Fabritius MP, Schuler F, Dorn F, et al. Crossed cerebellar diaschisis in acute ischemic stroke: impact on morphologic and functional outcome. J Cereb Blood Flow Metab 2017;37(11):3615–24. (271678X16686594). [4] Lim JS, Ryu YH, Kim BM, Lee JD. Crossed cerebellar diaschisis due to intracranial hematoma in basal ganglia or thalamus. J Nucl Med 1998;39(12):2044–7. [5] Bailly P, Bazire A, Prat G, Ben Salem D. Crossed cerebellar diaschisis in status epilepticus. Presse Med 2017;46(1):117–8. [6] Calabria F, Schillaci O. Recurrent glioma and crossed cerebellar diaschisis in a patient examined with 18F-DOPA and 18F-FDG PET/CT. Clin Nucl Med 2012;37(9):878–9. [7] Mahale R, Mehta A, Rangasetty S. Crossed cerebellar diaschisis due to Rasmussen encephalitis. Pediatr Neurol 2015;53(3):272–3. [8] Gold L, Lauritzen M. Neuronal deactivation explains decreased cerebellar blood flow in response to focal cerebral ischemia or suppressed neocortical function. Proc Natl Acad Sci U S A 2002;99(11):7699–704. [9] Dettmers C, Hartmann A, Rommel T, Hartmann S, Pappata S, Baron JC. Contralateral cerebellar diaschisis 7 hours after MCA-occlusion in primates. Neurol Res 1995;17(2):109–12. [10] Seitz RJ, Azari NP, Knorr U, Binkofski F, Herzog H, Freund HJ. The role of diaschisis in stroke recovery. Stroke 1999;30(9):1844–50. [11] Szilagyi G, Vas A, Kerenyi L, Nagy Z, Csiba L, Gulyas B. Correlation between crossed cerebellar diaschisis and clinical neurological scales. Acta Neurol Scand 2012;125(6):373–81. [12] Di Piero V, Chollet F, Dolan RJ, Thomas DJ, Frackowiak R. The functional nature of cerebellar diaschisis. Stroke 1990;21(9):1365–9. [13] Fu J, Chen WJ, Wu GY, Cheng JL, Wang MH, Zhuge Q, et al. Whole-brain 320detector row dynamic volume CT perfusion detected crossed cerebellar diaschisis after spontaneous intracerebral hemorrhage. Neuroradiology 2015;57(2):179–87. [14] Haller S, Zaharchuk G, Thomas DL, Lovblad KO, Barkhof F, Golay X. Arterial spin labeling perfusion of the brain: emerging clinical applications. Radiology 2016;281(2):337–56. [15] Dai W, Garcia D, de Bazelaire C, Alsop DC. Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magn Reson Med 2008;60(6):1488–97.
42