Yuhan Jiang1, Peipei Chang1, Yingqiu Liuyang1, Bingbing Gao1, Yiwei Che1, Renwang Pu1, Qingwei Song1, Ailian Liu1, Zhiwei Shen2, Jiazheng Wang2, and Yanwei Miao1
1the First Affiliated Hospital of Dalian Medical University, Dalian, China, 2Philips Healthcare, Beijing, China
Synopsis
Amide proton transfer weighted (APTw) MRI has
been increasingly applied in the study of stroke based on its ability to detect
pH and intracellular proteins content. In subacute infarction, the heterogeneity
of APTw signal may reflect the clinical treatment efficacy
of patients. In this study, we found that there is negative correlation between
the heterogeneity signals (APTwmax-min) in the ischemic regions and the
difference of NIHSS scores on the day of hospital admission and leaving (∆NIHSS). Therefore, the heterogeneity of APTw signal
is potentially an effective imaging biomarker to predict the
efficacy of patients with subacute cerebral infarction.
Introduction
Ischemic stroke
(IS) causes irreversible brain tissue infarction (infarct core, IC) and is the
main causes of death or dysfunction[1]. As a conventional IS
treatment, thrombolytic therapy increases the survival rate and reduce the
disability of patients with cerebral infarction. However, the time window of intravenous
thrombolysis for acute IS generally limited to within 4.5 hours after the onset
of symptoms. Unfortunately, clinically, there are a large proportion of patients
who fail to be sent to hospital within the "golden time". Studies
have shown that ischemic penumbra (IP) may still exist in this phase[2]. As a branch of the
chemical exchange saturation transfer (CEST) imaging method[3], amide proton
transfer weighted (APTw) MRI has been increasingly applied in the study of IS to
detect the changes of pH and intracellular proteins content.
Recent
studies have shown that APTw can be used to assess the severity of stroke and
predict the long-term clinical outcome of AIS patients[4]. The heterogeneity
of APTw signals can also be used as a biomarker to indicate prognosis. Therefore,
evaluating the heterogeneity of APTw signal in ischemic tissue is of great
significance for guiding clinical treatment.
The goal
of this study was to determine whether lower APTw signal
heterogeneity in the ischemic regions of subacute infarction patients with better
clinical efficacy, and the influencing factors of the APTw signal heterogeneity.Methods
Twenty-three
patients (mean age: 64.00 ± 10.70, range: 44-86 years; 14 male) were
prospectively enrolled into this study from April 2019 to September 2019. All
MR images were acquired on a 3.0-T MRI scanner (Ingenia CX, Philips Healthcare,
Best, the Netherlands) with a 32-channel receive-only head coil. MR
protocols and scan parameters were shown in Table 1. After
scanning, all raw data were automatically transmitted to a workstation
(IntelliSpace Portal, ISP, Philips healthcare, Netherlands) to generate CBF map
and APTw map, and then measured independently by two radiologists with more
than 5 years of diagnostic experience.
IC was
determined according to the high signal intensity on DWI and IP
was defined as CBF-DWI mismatch area. APTw and CBF images were registered and overlaid
with the DWI maps. 3D ROIs of IC and IP
in APTw and CBF maps were semi-automatically drawn and fusion (Figure 1).
Then the mean APTw signal intensity of the ischemic area (APTwmean),
the relative cerebral blood flow (rCBFlesion) values and 3D volumes of
IC and IP were measured. Other APTw signals were also recorded including the
maximum APTw (APTwmax) and the minimum APTw (APTwmin). The
APTw signal heterogeneity were calculated as the difference of the maximum APTw
signal and the minimum values (APTwmax - APTwmin) [5].
NIHSS
score of all patients were evaluated by at least a neurologist when they were
admitted to the hospital (NIHSSadm) and discharged (NIHSSdis).
∆NIHSS was calculated as NIHSSadm - NIHSSdis.
All
statistical analyses were performed using the SPSS 22.0 software package. The
interclass correlation coefficient (ICC) was used to evaluate measurement
consistency between the two observers. The Pearson
correlation test was applied to analyze the correlation between APTw signals
and clinical-radiological findings. For all tests, values of P < 0.05
were considered to indicate statistical significance.Results
Measurement
consistency between the two observers was good (ICC > 0.75). APTwmax-min
signal were significantly lower in the IC and IP than the contralateral mirror side
(P < 0.01) (Fig 2a-2b). APTwmax-min
signal were significantly increased in the IP than the IC (P < 0.01)
(Fig 2b). But there are no significant differences of APTwmean
signal between the bilateral
sides both in IC and IP. Pearson correlation test of the relationship between the APTwmax-min
signal and ∆NIHSS score (Fig 3). The negative correlation was found
between the ∆NIHSS score and APTwmax-min within IC (R2 =
0.184, P = 0.041) and IP (R2 = 0.255, P = 0.014). Discussion
In this
study, we found that APTwmax-min in the IC and IP inversely correlated
with the ∆NIHSS scores with significant statistic difference. The results
indicate that the heterogeneity of APTw signals could assess the severity of
cerebral infarction patients, and then reflect the efficacy of supportive
treatment. The possible reasons for the
inhomogeneity of APTw signals may contribute from the destruction of blood-brain
barrier (BBB)[6], which will be seriously
influence the prognosis of patients with cerebral infarction[7]. Furthermore, unlike
hyperacute and acute infarction, the pathophysiological mechanism of subacute
infarction is complicated, and the influencing factors of APTw signals should
not be limited to the changes in tissue pH[8]. In
general, patients with low APTw signal heterogeneity had a significant
improvement in the severity of clinical symptoms when they were discharged from
the hospital. Therefore, the heterogeneity of APTw signal can be used as a
potential imaging marker to judge the severity and efficacy of cerebral
infarction.Conclusion
Lower
APTw signal heterogeneity in the ischemic regions of subacute infarction
patients is a significant predictor of the clinical efficacy. It will have benefits
in prediction of clinical treatment for patients with advanced thrombolytic
therapy.Acknowledgements
No acknowledgement found.References
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