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  1. Yong CW, Lai KW, Murphy BP, Hum YC
    Curr Med Imaging, 2021;17(8):981-987.
    PMID: 33319690 DOI: 10.2174/1573405616666201214122409
    BACKGROUND: Osteoarthritis (OA) is a common degenerative joint inflammation that may lead to disability. Although OA is not lethal, this disease will remarkably affect patient's mobility and their daily lives. Detecting OA at an early stage allows for early intervention and may slow down disease progression.

    INTRODUCTION: Magnetic resonance imaging is a useful technique to visualize soft tissues within the knee joint. Cartilage delineation in magnetic resonance (MR) images helps in understanding the disease progressions. Convolutional neural networks (CNNs) have shown promising results in computer vision tasks, and various encoder-decoder-based segmentation neural networks are introduced in the last few years. However, the performances of such networks are unknown in the context of cartilage delineation.

    METHODS: This study trained and compared 10 encoder-decoder-based CNNs in performing cartilage delineation from knee MR images. The knee MR images are obtained from the Osteoarthritis Initiative (OAI). The benchmarking process is to compare various CNNs based on physical specifications and segmentation performances.

    RESULTS: LadderNet has the least trainable parameters with the model size of 5 MB. UNetVanilla crowned the best performances by having 0.8369, 0.9108, and 0.9097 on JSC, DSC, and MCC.

    CONCLUSION: UNetVanilla can be served as a benchmark for cartilage delineation in knee MR images, while LadderNet served as an alternative if there are hardware limitations during production.

  2. Shoaib MA, Hossain MB, Hum YC, Chuah JH, Mohd Salim MI, Lai KW
    Curr Med Imaging, 2020;16(6):739-751.
    PMID: 32723246 DOI: 10.2174/1573405615666190903143330
    BACKGROUND: Ultrasound (US) imaging can be a convenient and reliable substitute for magnetic resonance imaging in the investigation or screening of articular cartilage injury. However, US images suffer from two main impediments, i.e., low contrast ratio and presence of speckle noise.

    AIMS: A variation of anisotropic diffusion is proposed that can reduce speckle noise without compromising the image quality of the edges and other important details.

    METHODS: For this technique, four gradient thresholds were adopted instead of one. A new diffusivity function that preserves the edge of the resultant image is also proposed. To automatically terminate the iterative procedures, the Mean Absolute Error as its stopping criterion was implemented.

    RESULTS: Numerical results obtained by simulations unanimously indicate that the proposed method outperforms conventional speckle reduction techniques. Nevertheless, this preliminary study has been conducted based on a small number of asymptomatic subjects.

    CONCLUSION: Future work must investigate the feasibility of this method in a large cohort and its clinical validity through testing subjects with a symptomatic cartilage injury.

  3. Foo LS, Yap WS, Hum YC, Manan HA, Tee YK
    J Magn Reson, 2020 01;310:106648.
    PMID: 31760147 DOI: 10.1016/j.jmr.2019.106648
    Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) holds great potential to provide new metabolic information for clinical applications such as tumor, stroke and Parkinson's Disease diagnosis. Many active research and developments have been conducted to translate this emerging MRI technique for routine clinical applications. In general, there are two CEST quantification techniques: (i) model-free and (ii) model-based techniques. The reliability of these quantification techniques depends heavily on the experimental conditions and quality of the collected data. Errors such as noise may lead to misleading quantification results and thus inaccurate diagnosis when CEST imaging becomes a standard or routine imaging scan in the future. This paper investigates the accuracy and robustness of these quantification techniques under different signal-to-noise (SNR) levels and magnetic field strengths. The quantified CEST effect before and after adding random Gaussian White Noise using model-free and model-based quantification techniques were compared. It was found that the model-free technique consistently yielded larger average percentage error across all tested parameters compared to its model-based counterpart, and that the model-based technique could withstand SNR of about 3 times lower than the model-free technique. When applied on noisy brain tumor, ischemic stroke, and Parkinson's Disease clinical data, the model-free technique failed to produce significant differences between normal and abnormal tissue whereas the model-based technique consistently generated significant differences. Although the model-free technique was less accurate and robust, its simplicity and thus speed would still make it a good approximate when the SNR was high (>50) or when the CEST effect was large and well-defined. For more accurate CEST quantification, model-based techniques should be considered. When SNR was low (<50) and the CEST effect was small such as those acquired from clinical field strength scanners, which are generally 3T and below, model-based techniques should be considered over model-free counterpart to maintain an average percentage error of less than 44% even under very noisy condition as tested in this work.
  4. Yeoh PSQ, Lai KW, Goh SL, Hasikin K, Hum YC, Tee YK, et al.
    Comput Intell Neurosci, 2021;2021:4931437.
    PMID: 34804143 DOI: 10.1155/2021/4931437
    Osteoarthritis (OA), especially knee OA, is the most common form of arthritis, causing significant disability in patients worldwide. Manual diagnosis, segmentation, and annotations of knee joints remain as the popular method to diagnose OA in clinical practices, although they are tedious and greatly subject to user variation. Therefore, to overcome the limitations of the commonly used method as above, numerous deep learning approaches, especially the convolutional neural network (CNN), have been developed to improve the clinical workflow efficiency. Medical imaging processes, especially those that produce 3-dimensional (3D) images such as MRI, possess ability to reveal hidden structures in a volumetric view. Acknowledging that changes in a knee joint is a 3D complexity, 3D CNN has been employed to analyse the joint problem for a more accurate diagnosis in the recent years. In this review, we provide a broad overview on the current 2D and 3D CNN approaches in the OA research field. We reviewed 74 studies related to classification and segmentation of knee osteoarthritis from the Web of Science database and discussed the various state-of-the-art deep learning approaches proposed. We highlighted the potential and possibility of 3D CNN in the knee osteoarthritis field. We concluded by discussing the possible challenges faced as well as the potential advancements in adopting 3D CNNs in this field.
  5. Koo JC, Ke Q, Hum YC, Goh CH, Lai KW, Yap WS, et al.
    Quant Imaging Med Surg, 2023 Sep 01;13(9):5902-5920.
    PMID: 37711826 DOI: 10.21037/qims-23-46
    BACKGROUND: Renal cancer is one of the leading causes of cancer-related deaths worldwide, and early detection of renal cancer can significantly improve the patients' survival rate. However, the manual analysis of renal tissue in the current clinical practices is labor-intensive, prone to inter-pathologist variations and easy to miss the important cancer markers, especially in the early stage.

    METHODS: In this work, we developed deep convolutional neural network (CNN) based heterogeneous ensemble models for automated analysis of renal histopathological images without detailed annotations. The proposed method would first segment the histopathological tissue into patches with different magnification factors, then classify the generated patches into normal and tumor tissues using the pre-trained CNNs and lastly perform the deep ensemble learning to determine the final classification. The heterogeneous ensemble models consisted of CNN models from five deep learning architectures, namely VGG, ResNet, DenseNet, MobileNet, and EfficientNet. These CNN models were fine-tuned and used as base learners, they exhibited different performances and had great diversity in histopathological image analysis. The CNN models with superior classification accuracy (Acc) were then selected to undergo ensemble learning for the final classification. The performance of the investigated ensemble approaches was evaluated against the state-of-the-art literature.

    RESULTS: The performance evaluation demonstrated the superiority of the proposed best performing ensembled model: five-CNN based weighted averaging model, with an Acc (99%), specificity (Sp) (98%), F1-score (F1) (99%) and area under the receiver operating characteristic (ROC) curve (98%) but slightly inferior recall (Re) (99%) compared to the literature.

    CONCLUSIONS: The outstanding robustness of the developed ensemble model with a superiorly high-performance scores in the evaluated metrics suggested its reliability as a diagnosis system for assisting the pathologists in analyzing the renal histopathological tissues. It is expected that the proposed ensemble deep CNN models can greatly improve the early detection of renal cancer by making the diagnosis process more efficient, and less misdetection and misdiagnosis; subsequently, leading to higher patients' survival rate.

  6. Voon W, Hum YC, Tee YK, Yap WS, Nisar H, Mokayed H, et al.
    Sci Rep, 2023 Nov 22;13(1):20518.
    PMID: 37993544 DOI: 10.1038/s41598-023-46619-6
    Debates persist regarding the impact of Stain Normalization (SN) on recent breast cancer histopathological studies. While some studies propose no influence on classification outcomes, others argue for improvement. This study aims to assess the efficacy of SN in breast cancer histopathological classification, specifically focusing on Invasive Ductal Carcinoma (IDC) grading using Convolutional Neural Networks (CNNs). The null hypothesis asserts that SN has no effect on the accuracy of CNN-based IDC grading, while the alternative hypothesis suggests the contrary. We evaluated six SN techniques, with five templates selected as target images for the conventional SN techniques. We also utilized seven ImageNet pre-trained CNNs for IDC grading. The performance of models trained with and without SN was compared to discern the influence of SN on classification outcomes. The analysis unveiled a p-value of 0.11, indicating no statistically significant difference in Balanced Accuracy Scores between models trained with StainGAN-normalized images, achieving a score of 0.9196 (the best-performing SN technique), and models trained with non-normalized images, which scored 0.9308. As a result, we did not reject the null hypothesis, indicating that we found no evidence to support a significant discrepancy in effectiveness between stain-normalized and non-normalized datasets for IDC grading tasks. This study demonstrates that SN has a limited impact on IDC grading, challenging the assumption of performance enhancement through SN.
  7. Teo K, Yong CW, Chuah JH, Hum YC, Tee YK, Xia K, et al.
    Arab J Sci Eng, 2021 Aug 16.
    PMID: 34422543 DOI: 10.1007/s13369-021-06040-5
    Hospital readmission shortly after discharge threatens the quality of patient care and leads to increased medical care costs. In the United States, hospitals with high readmission rates are subject to federal financial penalties. This concern calls for incentives for healthcare facilities to reduce their readmission rates by predicting patients who are at high risk of readmission. Conventional practices involve the use of rule-based assessment scores and traditional statistical methods, such as logistic regression, in developing risk prediction models. The recent advancements in machine learning driven by improved computing power and sophisticated algorithms have the potential to produce highly accurate predictions. However, the value of such models could be overrated. Meanwhile, the use of other flexible models that leverage simple algorithms offer great transparency in terms of feature interpretation, which is beneficial in clinical settings. This work presents an overview of the current trends in risk prediction models developed in the field of readmission. The various techniques adopted by researchers in recent years are described, and the topic of whether complex models outperform simple ones in readmission risk stratification is investigated.
  8. Pan SQ, Hum YC, Lai KW, Yap WS, Ong CW, Tee YK
    Magn Reson Med Sci, 2024 Aug 14.
    PMID: 39143021 DOI: 10.2463/mrms.tn.2024-0069
    The quantitative analysis of pulsed-chemical exchange saturation transfer (CEST) using a full model-based method is computationally challenging, as it involves dealing with varying RF values in pulsed saturation. A power equivalent continuous approximation of B1 power was usually applied to accelerate the analysis. In line with recent consensus recommendations from the CEST community for pulsed-CEST at 3T, particularly recommending a high RF saturation power (B1 = 2.0 µT) for the clinical application in brain tumors, this technical note investigated the feasibility of using average power (AP) as the continuous approximation. The simulated results revealed excellent performance of the AP continuous approximation in low saturation power scenarios, but discrepancies were observed in the z-spectra for the high saturation power cases. Cautions should be taken, or it may lead to inaccurate fitted parameters, and the difference can be more than 10% in the high saturation power cases.
  9. Manaf NA, Aziz MN, Ridzuan DS, Mohamad Salim MI, Wahab AA, Lai KW, et al.
    Med Biol Eng Comput, 2016 Jun;54(6):967-81.
    PMID: 27039402 DOI: 10.1007/s11517-016-1480-2
    Recently, there is an increasing interest in the use of local hyperthermia treatment for a variety of clinical applications. The desired therapeutic outcome in local hyperthermia treatment is achieved by raising the local temperature to surpass the tissue coagulation threshold, resulting in tissue necrosis. In oncology, local hyperthermia is used as an effective way to destroy cancerous tissues and is said to have the potential to replace conventional treatment regime like surgery, chemotherapy or radiotherapy. However, the inability to closely monitor temperature elevations from hyperthermia treatment in real time with high accuracy continues to limit its clinical applicability. Local hyperthermia treatment requires real-time monitoring system to observe the progression of the destroyed tissue during and after the treatment. Ultrasound is one of the modalities that have great potential for local hyperthermia monitoring, as it is non-ionizing, convenient and has relatively simple signal processing requirement compared to magnetic resonance imaging and computed tomography. In a two-dimensional ultrasound imaging system, changes in tissue microstructure during local hyperthermia treatment are observed in terms of pixel value analysis extracted from the ultrasound image itself. Although 2D ultrasound has shown to be the most widely used system for monitoring hyperthermia in ultrasound imaging family, 1D ultrasound on the other hand could offer a real-time monitoring and the method enables quantitative measurement to be conducted faster and with simpler measurement instrument. Therefore, this paper proposes a new local hyperthermia monitoring method that is based on one-dimensional ultrasound. Specifically, the study investigates the effect of ultrasound attenuation in normal and pathological breast tissue when the temperature in tissue is varied between 37 and 65 °C during local hyperthermia treatment. Besides that, the total protein content measurement was also conducted to investigate the relationship between attenuation and tissue denaturation level at different temperature ranges. The tissues were grouped according to their histology results, namely normal tissue with large predominance of cells (NPC), cancer tissue with large predominance of cells (CPC) and cancer with high collagen fiber content (CHF). The result shows that the attenuation coefficient of ultrasound measured following the local hyperthermia treatment increases with the increment of collagen fiber content in tissue as the CHF attenuated ultrasound at the highest rate, followed by NPC and CPC. Additionally, the attenuation increment is more pronounced at the temperature over 55 °C. This describes that the ultrasound wave experienced more energy loss when it propagates through a heated tissue as the tissue structure changes due to protein coagulation effect. Additionally, a significant increase in the sensitivity of attenuation to protein denaturation is also observed with the highest sensitivity obtained in monitoring NPC. Overall, it is concluded that one-dimensional ultrasound can be used as a monitoring method of local hyperthermia since its attenuation is very sensitive to the changes in tissue microstructure during hyperthermia.
  10. Foo LS, Harston G, Mehndiratta A, Yap WS, Hum YC, Lai KW, et al.
    Quant Imaging Med Surg, 2021 Aug;11(8):3797-3811.
    PMID: 34341751 DOI: 10.21037/qims-20-1339
    Amide proton transfer (APT) magnetic resonance imaging (MRI) is a pH-sensitive imaging technique that can potentially complement existing clinical imaging protocol for the assessment of ischemic stroke. This review aims to summarize the developments in the clinical research of APT imaging of ischemic stroke after 17 years of progress since its first preclinical study in 2003. Three electronic databases: PubMed, Scopus, and Cochrane Library were systematically searched for articles reporting clinical studies on APT imaging of ischemic stroke. Only articles in English published between 2003 to 2020 that involved patients presenting ischemic stroke-like symptoms that underwent APT MRI were included. Of 1,093 articles screened, 14 articles met the inclusion criteria with a total of 282 patients that had been scanned using APT imaging. Generally, the clinical studies agreed APT effect to be hypointense in ischemic tissue compared to healthy tissue, allowing for the detection of ischemic stroke. Other uses of APT imaging have also been investigated in the studies, including penumbra identification, predicting long term clinical outcome, and serving as a biomarker for supportive treatment monitoring. The published results demonstrated the potential of APT imaging in these applications, but further investigations and larger trials are needed for conclusive evidence. Future studies are recommended to report the result of asymmetry analysis at 3.5 ppm along with the findings of the study to reduce this contribution to the heterogeneity of experimental methods observed and to facilitate effective comparison of results between studies and centers. In addition, it is important to focus on the development of fast 3D imaging for full volumetric ischemic tissue assessment for clinical translation.
  11. Meng LK, Khalil A, Ahmad Nizar MH, Nisham MK, Pingguan-Murphy B, Hum YC, et al.
    Curr Med Imaging Rev, 2019;15(10):983-989.
    PMID: 32008525 DOI: 10.2174/1573405615666190724101600
    BACKGROUND: Bone Age Assessment (BAA) refers to a clinical procedure that aims to identify a discrepancy between biological and chronological age of an individual by assessing the bone age growth. Currently, there are two main methods of executing BAA which are known as Greulich-Pyle and Tanner-Whitehouse techniques. Both techniques involve a manual and qualitative assessment of hand and wrist radiographs, resulting in intra and inter-operator variability accuracy and time-consuming. An automatic segmentation can be applied to the radiographs, providing the physician with more accurate delineation of the carpal bone and accurate quantitative analysis.

    METHODS: In this study, we proposed an image feature extraction technique based on image segmentation with the fully convolutional neural network with eight stride pixel (FCN-8). A total of 290 radiographic images including both female and the male subject of age ranging from 0 to 18 were manually segmented and trained using FCN-8.

    RESULTS AND CONCLUSION: The results exhibit a high training accuracy value of 99.68% and a loss rate of 0.008619 for 50 epochs of training. The experiments compared 58 images against the gold standard ground truth images. The accuracy of our fully automated segmentation technique is 0.78 ± 0.06, 1.56 ±0.30 mm and 98.02% in terms of Dice Coefficient, Hausdorff Distance, and overall qualitative carpal recognition accuracy, respectively.

  12. Voon W, Hum YC, Tee YK, Yap WS, Salim MIM, Tan TS, et al.
    Sci Rep, 2022 Nov 10;12(1):19200.
    PMID: 36357456 DOI: 10.1038/s41598-022-21848-3
    Computer-aided Invasive Ductal Carcinoma (IDC) grading classification systems based on deep learning have shown that deep learning may achieve reliable accuracy in IDC grade classification using histopathology images. However, there is a dearth of comprehensive performance comparisons of Convolutional Neural Network (CNN) designs on IDC in the literature. As such, we would like to conduct a comparison analysis of the performance of seven selected CNN models: EfficientNetB0, EfficientNetV2B0, EfficientNetV2B0-21k, ResNetV1-50, ResNetV2-50, MobileNetV1, and MobileNetV2 with transfer learning. To implement each pre-trained CNN architecture, we deployed the corresponded feature vector available from the TensorFlowHub, integrating it with dropout and dense layers to form a complete CNN model. Our findings indicated that the EfficientNetV2B0-21k (0.72B Floating-Point Operations and 7.1 M parameters) outperformed other CNN models in the IDC grading task. Nevertheless, we discovered that practically all selected CNN models perform well in the IDC grading task, with an average balanced accuracy of 0.936 ± 0.0189 on the cross-validation set and 0.9308 ± 0.0211on the test set.
  13. Shoaib MA, Chuah JH, Ali R, Hasikin K, Khalil A, Hum YC, et al.
    Comput Intell Neurosci, 2023;2023:4208231.
    PMID: 36756163 DOI: 10.1155/2023/4208231
    Cardiac health diseases are one of the key causes of death around the globe. The number of heart patients has considerably increased during the pandemic. Therefore, it is crucial to assess and analyze the medical and cardiac images. Deep learning architectures, specifically convolutional neural networks have profoundly become the primary choice for the assessment of cardiac medical images. The left ventricle is a vital part of the cardiovascular system where the boundary and size perform a significant role in the evaluation of cardiac function. Due to automatic segmentation and good promising results, the left ventricle segmentation using deep learning has attracted a lot of attention. This article presents a critical review of deep learning methods used for the left ventricle segmentation from frequently used imaging modalities including magnetic resonance images, ultrasound, and computer tomography. This study also demonstrates the details of the network architecture, software, and hardware used for training along with publicly available cardiac image datasets and self-prepared dataset details incorporated. The summary of the evaluation matrices with results used by different researchers is also presented in this study. Finally, all this information is summarized and comprehended in order to assist the readers to understand the motivation and methodology of various deep learning models, as well as exploring potential solutions to future challenges in LV segmentation.
  14. Jamaludin MR, Lai KW, Chuah JH, Zaki MA, Hum YC, Tee YK, et al.
    Behav Neurol, 2021;2021:2684855.
    PMID: 34777631 DOI: 10.1155/2021/2684855
    Spine surgeries impose risk to the spine's surrounding anatomical and physiological structures especially the spinal cord and the nerve roots. Intraoperative neuromonitoring (IONM) is a technology developed to monitor the integrity of the spinal cord and the nerve roots via the surgery. Transcranial motor evoked potential (TcMEP) (one of the IONM modalities) is adopted to monitor the integrity of the motor pathway of the spinal cord and the motor nerve roots. Recent research suggested that the IONM is conducive as a prognostic tool towards the patient's functional outcome. This paper summarizes the researches of IONM being adopted as a prognostic tool. In addition, this paper highlights the problems associated with the signal parameters as the improvement criteria in the previous researches. Lastly, we review the challenges of TcMEP to achieve a prognostic tool focusing on the factors that could interfere with the generation of a stable TcMEP response. The final section will discuss recommendations for IONM technology to achieve an objective prognostic tool.
  15. Foo LS, Larkin JR, Sutherland BA, Ray KJ, Yap WS, Hum YC, et al.
    Magn Reson Med, 2021 04;85(4):2188-2200.
    PMID: 33107119 DOI: 10.1002/mrm.28565
    PURPOSE: To assess the correlation and differences between common amide proton transfer (APT) quantification methods in the diagnosis of ischemic stroke.

    METHODS: Five APT quantification methods, including asymmetry analysis and its variants as well as two Lorentzian model-based methods, were applied to data acquired from six rats that underwent middle cerebral artery occlusion scanned at 9.4T. Diffusion and perfusion-weighted images, and water relaxation time maps were also acquired to study the relationship of these conventional imaging modalities with the different APT quantification methods.

    RESULTS: The APT ischemic area estimates had varying sizes (Jaccard index: 0.544 ≤ J ≤ 0.971) and had varying correlations in their distributions (Pearson correlation coefficient: 0.104 ≤ r ≤ 0.995), revealing discrepancies in the quantified ischemic areas. The Lorentzian methods produced the highest contrast-to-noise ratios (CNRs; 1.427 ≤ CNR ≤ 2.002), but generated APT ischemic areas that were comparable in size to the cerebral blood flow (CBF) deficit areas; asymmetry analysis and its variants produced APT ischemic areas that were smaller than the CBF deficit areas but larger than the apparent diffusion coefficient deficit areas, though having lower CNRs (0.561 ≤ CNR ≤ 1.083).

    CONCLUSION: There is a need to further investigate the accuracy and correlation of each quantification method with the pathophysiology using a larger scale multi-imaging modality and multi-time-point clinical study. Future studies should include the magnetization transfer ratio asymmetry results alongside the findings of the study to facilitate the comparison of results between different centers and also the published literature.

  16. Haw YH, Lai KW, Chuah JH, Bejo SK, Husin NA, Hum YC, et al.
    PeerJ Comput Sci, 2023;9:e1325.
    PMID: 37346512 DOI: 10.7717/peerj-cs.1325
    Oil palm is a key agricultural resource in Malaysia. However, palm disease, most prominently basal stem rot caused at least RM 255 million of annual economic loss. Basal stem rot is caused by a fungus known as Ganoderma boninense. An infected tree shows few symptoms during early stage of infection, while potentially suffers an 80% lifetime yield loss and the tree may be dead within 2 years. Early detection of basal stem rot is crucial since disease control efforts can be done. Laboratory BSR detection methods are effective, but the methods have accuracy, biosafety, and cost concerns. This review article consists of scientific articles related to the oil palm tree disease, basal stem rot, Ganoderma Boninense, remote sensors and deep learning that are listed in the Web of Science since year 2012. About 110 scientific articles were found that is related to the index terms mentioned and 60 research articles were found to be related to the objective of this research thus included in this review article. From the review, it was found that the potential use of deep learning methods were rarely explored. Some research showed unsatisfactory results due to limitations on dataset. However, based on studies related to other plant diseases, deep learning in combination with data augmentation techniques showed great potentials, showing remarkable detection accuracy. Therefore, the feasibility of analyzing oil palm remote sensor data using deep learning models together with data augmentation techniques should be studied. On a commercial scale, deep learning used together with remote sensors and unmanned aerial vehicle technologies showed great potential in the detection of basal stem rot disease.
  17. Foo LS, Larkin JR, Sutherland BA, Ray KJ, Yap WS, Goh CH, et al.
    Quant Imaging Med Surg, 2023 Dec 01;13(12):7879-7892.
    PMID: 38106293 DOI: 10.21037/qims-23-510
    BACKGROUND: When an ischemic stroke happens, it triggers a complex signalling cascade that may eventually lead to neuronal cell death if no reperfusion. Recently, the relayed nuclear Overhauser enhancement effect at -1.6 ppm [NOE(-1.6 ppm)] has been postulated may allow for a more in-depth analysis of the ischemic injury. This study assessed the potential utility of NOE(-1.6 ppm) in an ischemic stroke model.

    METHODS: Diffusion-weighted imaging, perfusion-weighted imaging, and chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) data were acquired from five rats that underwent scans at 9.4 T after middle cerebral artery occlusion.

    RESULTS: The apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and apparent exchange-dependent relaxations (AREX) at 3.5 ppm and NOE(-1.6 ppm) were quantified. AREX(3.5 ppm) and NOE(-1.6 ppm) were found to be hypointense and exhibited different signal patterns within the ischemic tissue. The NOE(-1.6 ppm) deficit areas were equal to or larger than the ADC deficit areas, but smaller than the AREX(3.5 ppm) deficit areas. This suggested that NOE(-1.6 ppm) might further delineate the acidotic tissue estimated using AREX(3.5 ppm). Since NOE(-1.6 ppm) is closely related to membrane phospholipids, NOE(-1.6 ppm) potentially highlighted at-risk tissue affected by lipid peroxidation and membrane damage. Altogether, the ADC/NOE(-1.6 ppm)/AREX(3.5 ppm)/CBF mismatches revealed four zones of increasing sizes within the ischemic tissue, potentially reflecting different pathophysiological information.

    CONCLUSIONS: Using CEST coupled with ADC and CBF, the ischemic tissue may thus potentially be separated into four zones to better understand the pathophysiology after stroke and improve ischemic tissue fate definition. Further verification of the potential utility of NOE(-1.6 ppm) may therefore lead to a more precise diagnosis.

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