Evaluation of Serial and Multisequence MRI Protocols for Glymphatic Imaging in Dogs : : A Comparative Study after Intravenous Contrast Administration = 개 글림프계 영상화를 위한 연속 및 다중 시퀀스 자기공명영상 프로토콜 평가: 정맥 내 조영제 투여 후 비교 연구

다국어 초록 (Multilingual Abstract)

To optimize intravenous-contrast glymphatic magnetic resonance imaging (MRI) in dogs, a serial T1-Weighted volumetric interpolated breath-hold examination (T1W VIBE) protocol (Protocol 1) and a multisequence protocol (Protocol 2) were acquired over 0–4 hours and at 24 hours. Changes in signal-to-noise ratio (ΔSNR) and changes in signal intensity (ΔS/S) were used to identify sequence-specific sensitivity and optimal post-imaging time for glymphatic system. Five clinically normal dogs (n=5) were scanned under general anesthesia in ventral recumbency. Gadobutrol (1.0 mmol/mL) was administered intravenously at 0.3 mL/kg. In protocol 1, T1W VIBE was acquired from 0–4 hours post-contrast, with a delayed scan at 24 hours. In protocol, the heavily T2-weighted Fluid-attenuated inversion recovery (hT2W-FLAIR), T1- weighted Spin Echo dynamic (T1W SE dynamic), T1- weighted Sampling perfection with application-optimized contrasts using different flip angle evolution (T1W SPACE), T1- weighted Magnetization-prepared rapid gradient echo (T1W MPRAGE), T2- weighted Turbo Spin Echo Fluid-attenuated inversion recovery (T2W TSE FLAIR), T2- weighted Sampling perfection with application-optimized contrasts using different flip angle evolution Fluid-attenuated inversion recovery (T2W SPACE FLAIR), and T1- weighted Sampling perfection with application-optimized contrasts using different flip angle evolution with blood-suppression (T1W SPACE with blood-suppression) were obtained. Quantitative assessments were performed on the submandibular lymph node, vitreous body, olfactory bulb, and brain base. Qualitative assessment focused the meningeal lymphatic vessels (MLVs), corpus callosum, fourth ventricle, perivascular spaces (PVS), and choroid plexus. Quantitatively, ΔSNR and change in signal intensity (ΔS/S) analyses revealed distinct signal kinetics across structures. In protocol 1 (T1W VIBE), ΔSNR in the submandibular lymph nodes increased sharply after contrast and declined within 2–4 hours, while the olfactory bulb and vitreous body showed gradual and delayed increases. In protocol 2 (T1W SE dynamic), overall patterns were similar but with clearer enhancement and greater variability in the brain base. At 24 hours, ΔSNR values returned near baseline, remaining slightly positive mainly in the lymph nodes. DSC imaging demonstrated rapid minute-scale uptake in the meningeal lymphatic vessels. Qualitative assessment revealed that the sequences providing the best visualization of each structure included Meningeal lymphatic vessels (MLVs), which were best visualized using T1W SE dynamic. T1W SE dynamic also provided optimal imaging for perivascular spaces (PVS) and the choroid plexus. The corpus callosum was best seen with T2W FLAIR, and for the fourth ventricle, the optimal sequences were T2W FLAIR (enhancement), T1W SE dynamic, and T1W SPACE (clarity). Pre-contrast presence was best assessed using T1W MPRAGE. This study represents the first canine glymphatic MRI using intravenous contrast. A 0–4 hours acquisition time with a delayed scan at 24 hours appears practical. Serial T1W VIBE provides reliable long-term kinetic tracking and inter-plane consistency for canine glymphatic MRI, while the multisequence protocol improves structural contrast and anatomical specificity. Through qualitative evaluation, we found that the combination of T1W SE dynamic and T2W FLAIR provided the most stable and practical approach for assessing the glymphatic system. By quantitative analyzing ΔSNR and ΔS/S, we quantified contrast inflow and clearance, establishing a foundation for CSF flow evaluation, early neurological disease detection, and clinical glymphatic MRI optimization.

국문 초록 (Abstract)

본 연구는 개에서 정맥 내 조영제를 이용한 글림프 자기공명영상(MRI)의 최적 촬영 조건을 규명하기 위해, 연속 T1 강조 볼류메트릭 인터폴레이션 브레스홀드 검사(T1W VIBE) 시퀀스(프로토콜 1)와 다중 시퀀스 프로토콜(프로토콜 2)을 0–4시간 및 24시간 시점에서 시행하였다. Δ신호대잡음비(ΔSNR)와 신호 강도 변화(ΔS/S)를 이용하여 시퀀스별 민감도와 최적 촬영 시점을 평가하였다. 임상적으로 정상인 개 5두를 전신마취 하에 배횡와위로 고정하여 촬영하였으며, gadobutrol(1.0 mmol/mL)을 0.3 mL/kg 용량으로 정맥 투여하였다. 프로토콜 1에서는 조영제 투여 후 0–4시간 동안 T1W VIBE를 연속 촬영하고, 24시간 지연 영상을 추가하였다. 프로토콜 2에서는 hT2W-FLAIR, T1W SE dynamic, T1W SPACE, T1W MPRAGE, T2W TSE FLAIR, T2W SPACE FLAIR, 혈류 억제 T1W SPACE를 획득하였다. 정량 평가는 턱밑 림프절, 유리체, 후각망울, 뇌바닥에서 수행하였고, 정성 평가는 뇌수막 림프관(MLVs), 뇌량, 제4뇌실, 혈관주위공간(PVS), 맥락총을 대상으로 하였다. 정량 분석에서 ΔSNR은 구조별로 상이한 신호 동역학을 보였다. 턱밑 림프절은 조영 후 급격히 증가한 뒤 2–4시간 사이 감소하였으며, 유리체와 후각망울은 점진적이고 지연된 증가 양상을 보였다. 뇌바닥은 개체 간 변동성이 컸다. 24시간 시점에서 ΔSNR은 대부분 기준선에 근접하였으며, 턱밑 림프절에서만 경미한 양의 값이 유지되었다. DSC 영상에서는 뇌수막 림프관에서 분 단위의 조기 조영 유입이 확인되었다. 정성 평가 결과, 뇌수막 림프관, 혈관주위공간, 맥락총은 T1W SE dynamic에서 가장 우수하게 시각화되었고, 뇌량은 T2W FLAIR에서 가장 명확하였다. 제4뇌실은 T2W FLAIR, T1W SE dynamic, T1W SPACE에서 최적의 평가가 가능하였으며, 조영 전 구조 평가는 T1W MPRAGE가 가장 적합하였다. 결론적으로, 0–4시간 촬영과 24시간 지연 촬영의 조합은 개 글림프 MRI에서 실용적인 표준 시간으로 판단된다. 연속 T1W VIBE는 장기 동역학 추적에 유용하며, 다중 시퀀스 프로토콜은 구조적 대비와 해부학적 특이성을 향상시킨다. ΔSNR 및 ΔS/S 기반 정량 분석은 조영제 유입과 제거를 객관적으로 평가할 수 있는 근거를 제공하며, 향후 뇌척수액 흐름 평가와 신경계 질환의 조기 진단을 위한 임상 글림프 MRI 최적화에 기여할 것으로 판단된다.

목차 (Table of Contents)

• INTRODUCTION 1
• A. Background 1
• B. Objective 9
• MATERIALS AND METHODS 11
• A. Animals 11
• B. MRI scan 12
• a). Protocol Design Overview 12
• b). Protocol 1: Continuous T1W VIBE 13
• c). Protocol 2: Multisequence protocol 14
• C. Image analysis 21
• a). Enhancement Visibility Gain 24
• b). Clarity with Surrounding Tissues 25
• c). Pre-contrast Presence 26
• D. Statistical analysis 32
• RESULTS 33
• A. Long-term quantitative evaluation (ΔSNR analysis) 34
• B. Short-term quantitative evaluation (DSC analysis) 41
• C. Qualitative evaluation 44
• a). Meningeal lymphatic vessels (MLVs) 44
• b). Corpus callosum 44
• c). 4th ventricle 45
• d). Perivascular spaces (PVS) 45
• e). Choroid plexus 46
• D. Sequence-specific structural visualization 91
• E. Time-dependent enhancement of ocular structures 97
• DISCUSSION 100
• A. Temporal Dynamics of Glymphatic Enhancement 100
• B. Imaging Planes and Glymphatic Pathways 101
• C. Rationale for ROI Selection in Canine Glymphatic Imaging 103
• D. Evaluation of T1W SE dynamic Sequence for Glymphatic Imaging 105
• E. Olfactory Bulb and Cribriform Plate Pathways in Glymphatic Transport 106
• F. T1W SPACE Blood-Suppression Sequence for Enhanced Glymphatic Visualization 108
• G. T1W MPRAGE for Brain Structure Visualization and BBB Leakage Detection 109
• H. hT2W FLAIR for Ocular and Periorbital Structure Visualization 110
• I. Quantitative Analysis of Glymphatic-Related Structures and Temporal Enhancement Patterns 111
• J. Methodological Considerations in Protocol Design 112
• K. Technical Artifacts and Signal Interpretation 113
• L. Overall interpretation 114
• M. Study Limitations 116
• N. Future Directions 117
• CONCLUSION 120
• References 121
• 국문초록 130