DOI: https://doi.org/10.2463/mrms.rev.2023-0175
PMID: https://pubmed.ncbi.nlm.nih.gov/38569866
تاريخ النشر: 2024-01-01
تحليل صور موتر الانتشار على طول الفضاء المحيط بالأوعية (DTI-ALPS): إعادة النظر في معنى وأهمية الطريقة
الملخص
لقد مرت أكثر من 5 سنوات منذ اقتراح طريقة تحليل صور الموجات الانتشارية على طول الفضاء المحيط بالأوعية الدموية (DTI-ALPS) بهدف تقييم النظام الغليمفاتي. هذه الطريقة مفيدة بسبب عدم تدخّلها، وتوفيرها لمؤشر بسيط في صيغة مباشرة، وإمكانية التحليل الرجعي. لذلك، تم اعتماد طريقة ALPS لتقييم النظام الغليمفاتي للعديد من الاضطرابات في العديد من الدراسات. الغرض من هذه المراجعة هو النظر إلى الوراء ومناقشة طريقة ALPS في هذه اللحظة.
تم العثور على مؤشر ALPS كدليل على عدد من الحالات المتعلقة بالنظام الغليمفاتي. وبالتالي، على الرغم من أن هذا كان متوقعًا في التقرير الأصلي، إلا أن نتائج طريقة ALPS غالبًا ما تُفسر على أنها تتعلق بشكل فريد بوظيفة النظام الغليمفاتي. ومع ذلك، أشارت عدد من الدراسات اللاحقة إلى المشاكل في تفسير البيانات. كما أنهم يشيرون بشكل صحيح، فإن ارتفاع مؤشر ALPS يدل على الحركة البراونية السائدة لجزيئات الماء في الاتجاه الشعاعي عند مستوى جسم البطين الجانبي، لا أكثر ولا أقل. لحسن الحظ، أصبح مصطلح “مؤشر ALPS” شائعًا ويعرف الآن كمصطلح شائع من قبل العديد من الباحثين. لذلك، يجب التعبير عن مؤشر ALPS ببساطة على أنه مرتفع أو منخفض، وما إذا كان يعكس نظامًا غليمفاتيًا من الأفضل مناقشته بعناية. بعبارة أخرى، عندما يتم ملاحظة انخفاض في مؤشر ALPS، يجب التعبير عنه على أنه “مؤشر ALPS منخفض” وليس مباشرة كـ “خلل في النظام الغليمفاتي”. مؤخرًا، تم اقتراح طرق مختلفة لتقييم النظام الغليمفاتي. وقد أصبح من الواضح أن هذه الطرق أيضًا لا تبدو أنها تعكس كمال النظام الغليمفاتي المعقد للغاية. وهذا يعني أنه سيكون من المرغوب استخدام طرق متنوعة بشكل مشترك لتقييم النظام الغليمفاتي بطريقة شاملة.
مقدمة

تم تقديم طريقة DTI-ALPS بالإضافة إلى عدة طرق أخرى لتقييم ديناميات السائل بين الخلايا بشكل غير جراحي، وقد تم الإبلاغ عن تطبيقها في أمراض وحالات مختلفة. تستعرض هذه المقالة الاتجاهات في دراسة النظام الغليمفاتي، مع التركيز على طريقة ALPS. تناقش المعنى والأهمية لهذه الطريقة وتستكشف كيفية استخدامها في هذا المجال.
مفهوم DTI-ALPS
الاتجاه الشعاعي، تحديدًا اليسار-اليمين أو
دقة صورة الانتشار، بوحدات المليمترات. فقط اتجاه الانتشار هو القابل للتمييز. ومع ذلك، ما تحاول طريقة ALPS تقييمه هو الحركة الكلية أو الماكروسكوبية للماء في اتجاه اتجاه PVS، وليس حركة الماء في PVS نفسه. وبالتالي، فإن هذه القيود ليست عائقًا أمام هذا المفهوم. بالإضافة إلى ذلك، نظرًا لأن الطريقة تستخدم صور الانتشار، فإنها تقيم “حركة” الماء، وليس “تدفق” الماء. وبالتالي، فإن حركة الماء نحو سطح الدماغ ونحو البطينات تخضع للتقييم بشكل متساوٍ. سيتم النظر في قضايا أخرى في قسم “الجدل في طريقة DTI-ALPS”.
تطبيق DTI-ALPS
طلب لمرض الزهايمر

طلب لمرض باركنسون وأمراض التنكس الأخرى
فقدان الخلايا العصبية الدوبامينية في المادة السوداء.

طلب لأمراض الأوعية الدموية الصغيرة
خلل وظيفي، وخلل حركي، وقد جذبت أيضًا الانتباه كحالة مرضية خلفية للأمراض التنكسية العصبية مثل مرض الزهايمر.
طلب لفرط الضغط الدماغي الطبيعي مجهول السبب
تحسنًا في الأعراض بعد جراحة التحويل، بينما لم يكن هناك زيادة ملحوظة في مؤشر ALPS بعد الجراحة في المجموعة التي لم تشهد تحسنًا في الأعراض (الشكل 4).
تطبيق لإصابة الدماغ الرضحية
تطبيق لمرض إزالة الميالين

ولا كانت مرتبطة بدرجات مقياس حالة الإعاقة الموسعة.
تطبيق للنوم

المعلمات مرتبطة إيجابيًا مع الاستيقاظ بعد بدء النوم وطول نوم حركة العين السريعة لدى المرضى الذين يعانون من النعاس من النوع 2.
النتائج حول الشيخوخة
ارتباط سلبي بين العمر ومؤشر ALPS في كبار السن الذين يعيشون في المجتمع والذين تتراوح أعمارهم من 60 عامًا وما فوق، مع معامل انحدار جزئي قياسي من
طرق أخرى لتقييم النظام اللمفاوي الدماغي
GBCA داخل السائل النخاعي
يعتبر استخدام دراسات المتعقب باستخدام التصوير بالرنين المغناطيسي مع مادة التباين المعطلة داخل السائل الشوكي (GBCA) هو المعيار الذهبي. ومع ذلك، يجب ملاحظة أن الوزن الجزيئي لمادة التباين المعطلة هو 0.6 كيلودالتون (Gadobtrol)، في حين أن وزن
GBCA عن طريق الوريد
| طريقة | تسلسل الرنين المغناطيسي | ظاهرة الهدف | موقع الهدف | الأدوار المفترضة في النظام الغليمفاتي |
| GBCA داخل السحايا | T1WI | اختراق عبر سطح الدماغ (المتتبع: GBCA) | سطح الدماغ | تدفق السائل الدماغي الشوكي إلى نسيج الدماغ |
| نفاذية الحاجز الدموي الدماغي (المتتبع: GBCA) | نسيج الدماغ | إنتاج ISF | ||
| GBCA عن طريق الوريد | T1WI | نفاذية جدار الوريد (المؤشر: GBCA) | وريد سطحي | حركة نفايات |
| تتبع GBCA | وعاء لمفاوي سحائي / الفضاء المحيط بالأوعية الدموية | حركة نفايات | ||
| وريدي
|
تسلسل الحالة المستقرة | نفاذية الحاجز الدموي الدماغي (المتتبع: الماء المعلم) | نسيج الدماغ | إنتاج ISF |
| دي تي آي – ألبس | DTI | الحركة البراونية لجزيء الماء في نسيج الدماغ | المادة البيضاء العميقة المجاورة للبُطين الجانبي | حركة السائل بين الأنسجة |
| تحليل مياه مجاني | DTI وغيرها. | زيادة نسبة الماء الحر | نسيج الدماغ | توسيع الفضاء بين الخلايا |
| حجم الفضاء المحيط بالأوعية | 3D-T2WI وغيرها. | توسع الفضاء المحيط بالأوعية | الفراغ المحيط بالأوعية | تراكم النفايات الأيضية |
| حجم المشيمية الوعائية | 3D-T1WI إلخ. | تضخم المشيمية | الضفيرة المشيمية | إزالة النفايات / رد الفعل المناعي إلخ. |
| ASL مع TI طويلة | ASL | نفاذية BBB (المؤشر: الماء المعلم) | نسيج الدماغ | إنتاج ISF |
| اقتران BOLD-CSF | جريء | تزامن النشاط العصبي وحركة الدماغ/السائل الدماغي الشوكي | نسيج الدماغ | البيئة الدقيقة للأنسجة |
| المرونة التصويرية | المرونة التصويرية | الخصائص اللزجة المرنة للدماغ | نسيج الدماغ | البيئة الدقيقة للأنسجة |
بعد إعطاء جرعة عادية من GBCA، لوحظ تسرب من الأوردة القشرية إلى السائل الدماغي الشوكي. تم ملاحظة تعزيز داخل المساحات المحيطة بالأوعية الدموية في العقد القاعدية وحول الأوردة القشرية بعد 4 ساعات من إعطاء GBCA عن طريق الوريد.
بعد إجراء IV-GBCA. كما درست الدراسة في الوقت نفسه تعزيز الفضاء المحيط بالأوعية الدموية في العقد القاعدية (PVS-BG)، وقد تم رؤية PVS-BG في 21 من 42 حالة.
تقييم تسرب الحاجز الدموي الدماغي. ومع ذلك، فإن تسرب الحاجز الدموي الدماغي من عوامل التباين المعتمدة على الجادولينيوم في الأنسجة الدماغية السليمة صغير جداً لدرجة أن القياس يتم تقييمه دائماً بالقرب من مستوى الضوضاء. في هذا الصدد، من المتوقع أن تتأثر القياسات بشكل كبير بتلوث الضوضاء، وظروف التصوير، وطرق التحليل. يجب أيضاً ملاحظة أن تقييم تسرب الحاجز الدموي الدماغي لا يقيم النظام الغليمفاتي بالكامل، بل جزءاً فقط من النظام بأكمله.
حجم الفضاء المحيط بالأوعية الدموية
اعتلال العين العصبي. أظهر رواد الفضاء الذين قضوا 6 أشهر في محطة الفضاء الدولية تضخمًا في الفضاءات المحيطة بالأوعية الدموية في العقد القاعدية والمادة البيضاء بعد رحلتهم في الفضاء. علاوة على ذلك، كان لدى رواد الفضاء الذين تطور لديهم اعتلال العين العصبي المرتبط برحلة الفضاء تضخم أكبر في الفضاءات المحيطة بالأوعية الدموية في المادة البيضاء مقارنةً بأولئك الذين لم يتطور لديهم المتلازمة، مما يشير إلى أن التغيرات طويلة الأمد في الجاذبية قد تؤثر على وظيفة النظام الغليمفاتي.
حجم المشيمية الوعائية
تم تحديد الدماغ وتنظيم تركيبة السائل الدماغي الشوكي لوظيفة الدماغ المتوازنة.
طرق الانتشار بخلاف طريقة ALPS
توسيم الدوران الشرياني
تصوير حركيات أنسجة الدماغ
كان الارتباط مرتبطًا بالتدهور المعرفي الذي لوحظ في المرضى الذين يعانون من مرض باركنسون. بالإضافة إلى ذلك، كان الارتباط المنخفض بين BOLD-CSF في مرضى باركنسون مرتبطًا بقشرة الحُقُب اليمنى الأرق.
طرق أخرى لدراسة المتتبعين
كان تراكم المادة المشعة خارج الجمجمة في القرينات الأنفية. في المرضى الذين يعانون من
اعتبار منهجية DTI-ALPS
وضع العائد على الاستثمار
إمكانية إعادة إنتاج طريقة ALPS

تعديل طريقة ALPS
وأظهرت تقنية التصوير بالرنين المغناطيسي ثلاثي المحاور ارتباطًا جيدًا. وهذا يشير إلى إمكانية استخدام طريقة DWI-ALPS مع MPG ثلاثي المحاور.
الامتحانات.
الجدل في طريقة DTI-ALPS
الخاتمة
كمصطلح شائع في هذا المجال البحثي. سيكون من الصحيح وصف مؤشر ALPS فقط بأنه مرتفع أو منخفض، زاد أو انخفض، وما إذا كان يعكس النظام الغليمفاتي أم لا يجب أن يعتبر موضوعًا للنقاش. بعبارة أخرى، إذا لوحظ انخفاض في مؤشر ALPS، يجب أن يقول عنوان الورقة “انخفاض في مؤشر ALPS” وليس “خلل في الغليمفاتي” مباشرة على الأقل في عنوان الورقة. فيما يتعلق بطريقة ALPS، ذكر البروفيسور إيلف أن “التغيرات في القياس تُرى في ظل ظروف حيث تتعطل وظيفة الغليمفاتي – لذا بينما ليس لدينا فهم قوي لطبيعة الإشارة بالضبط، يبدو أنها تعمل على مستوى ما” (تواصل شخصي)، ويتفق المؤلف مع رأيه.
تعارض المصالح
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Department of Innovative Biomedical Visualization (iBMV), Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
Department of Radiology, Nagoya University, Nagoya, Aichi, Japan
Department of Radiology, Aichi Medical University, Nagakute, Aichi, Japan
*Corresponding author: Department of Innovative Biomedical Visualization (iBMV), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. Phone: +81-52-744-2328, Fax: +81-52-744-2335, E-mail: ttaoka@med.nagoya-u.ac.jpThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives International License.
©2024 Japanese Society for Magnetic Resonance in Medicine
Received: December 25, 2023 | Accepted: February 22, 2024
DOI: https://doi.org/10.2463/mrms.rev.2023-0175
PMID: https://pubmed.ncbi.nlm.nih.gov/38569866
Publication Date: 2024-01-01
Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS): Revisiting the Meaning and Significance of the Method
Abstract
More than 5 years have passed since the Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS) method was proposed with the intention of evaluating the glymphatic system. This method is handy due to its noninvasiveness, provision of a simple index in a straightforward formula, and the possibility of retrospective analysis. Therefore, the ALPS method was adopted to evaluate the glymphatic system for many disorders in many studies. The purpose of this review is to look back and discuss the ALPS method at this moment.
The ALPS-index was found to be an indicator of a number of conditions related to the glymphatic system. Thus, although this was expected in the original report, the results of the ALPS method are often interpreted as uniquely corresponding to the function of the glymphatic system. However, a number of subsequent studies have pointed out the problems on the data interpretation. As they rightly point out, a higher ALPS-index indicates predominant Brownian motion of water molecules in the radial direction at the lateral ventricular body level, no more and no less. Fortunately, the term “ALPS-index” has become common and is now known as a common term by many researchers. Therefore, the ALPS-index should simply be expressed as high or low, and whether it reflects a glymphatic system is better to be discussed carefully. In other words, when a decreased ALPS-index is observed, it should be expressed as “decreased ALPS-index” and not directly as “glymphatic dysfunction”. Recently, various methods have been proposed to evaluate the glymphatic system. It has become clear that these methods also do not seem to reflect the entirety of the extremely complex glymphatic system. This means that it would be desirable to use various methods in combination to evaluate the glymphatic system in a comprehensive manner.
Introduction

the DTI-ALPS method but also several other approaches to noninvasively evaluate ISF dynamics have been introduced, and their application in various diseases and conditions has been reported. This article reviews trends in the study of the glymphatic system, with a focus on the ALPS method. It discusses the meaning and significance of this method and explores how it should be utilized in the field.
Concept of DTI-ALPS
radial direction, specifically the left-right or
resolution of the diffusion image, in units of millimeters. Only the direction of the diffusion is distinguishable. However, what the ALPS method is trying to evaluate is the total or macroscopic movement of water in the direction of the PVS direction, not the movement of water in the PVS itself. Thus, these limitations are not a hindrance to this concept. In addition, since the method uses diffusion images, it evaluates the “movement” of water, not the “flow” of water. Thus, water movement toward the brain surface and toward the ventricles is equally subject to evaluation. Other issues will be considered in “Controversy in DTI-ALPS method” section.
Application of DTI-ALPS
Application for Alzheimer’s disease

Application for Parkinson’s disease and other degenerative disease
loss of dopaminergic neurons in the substantia nigra.

Application for small vessel diseases
dysfunction, and motor dysfunction, and has also attracted attention as a background pathology for neurodegenerative diseases such as AD.
Application for idiopathic normal pressure hydrocephalus
symptomatic improvement after shunt surgery, whereas there was no significant increase in postoperative ALPSindex in the group without symptomatic improvement (Fig. 4).
Application for traumatic brain injury
Application for demyelinating disease

nor were they correlated with Expanded Disability Status Scale scores.
Application for sleep

parameters and positively correlated with wake after sleep onset and REM sleep length in patients with type 2 narcolepsy.
Findings on the aging
negative correlation between age and ALPS-index in com-munity-dwelling elderly aged 60 years and older, with a standard partial regression coefficient of
Other Methods for Evaluation of Glymphatic System
Intrathecal GBCA
humans, tracer studies using MR with intrathecal GBCA are considered to be the gold standard. However, it should be noted that the molecular weight of GBCA is 0.6 kDa (Gadobtrol), whereas that of
Intravenous GBCA
| Method | MR sequence | Target phenomenon | Target location | Assumed rolls in glymphatic system |
| Intrathecal GBCA | T1WI | Penetration via the brain surface (Tracer: GBCA) | Brain surface | CSF influx to brain parenchyma |
| BBB permeability (Tracer: GBCA) | Brain parenchyma | ISF production | ||
| Intravenous GBCA | T1WI | Venous wall permeability (Tracer: GBCA) | Surface vein | Movement of waste products |
| Tracking of GBCA | Meningeal lymphatic vessel/ Perivascular space | Movement of waste products | ||
| Intravenous
|
Steady-state sequence | BBB permeability (Tracer: labeled water) | Brain parenchyma | ISF production |
| DTI-ALPS | DTI | Brownian motion of the water molecule in the brain tissue | Deep white matter adjacent the lateral ventricle | Movement of ISF within the tissue |
| Free water analysis | DTI etc. | Increase of free water fraction | Brain parenchyma | Widening of interstitial space |
| Perivascular space volume | 3D-T2WI etc. | Dilatation of perivascular space | Perivascular space | Accumulation of metabolic waste |
| Choroid plexus volume | 3D-T1WI etc. | Enlargement of choroid plexus | Choroid plexus | Removal of waste/ Immune reaction etc. |
| ASL with long TI | ASL | BBB permeability (Tracer: tagged water) | Brain parenchyma | ISF production |
| BOLD-CSF coupling | BOLD | Synchrony of the neural activity and the brain/CSF motion | Brain parenchyma | Tissue microenvironment |
| Elastography | Elastography | Viscoelastic properties of the brain | Brain parenchyma | Tissue microenvironment |
human evaluation after administration of a normal dose of GBCA, leakage from the cortical veins into the CSF was observed. An enhancement within the PVS in the basal ganglia and around the cortical veins was observed after 4 h of IV-GBCA administration.
after IV-GBCA was performed. The study also simultaneously examined the enhancement of the basal ganglia perivascular space (PVS-BG), and PVS-BG was seen in 21 of the 42 cases.
evaluate BBB leakage. However, BBB leakage from GBCA in healthy brain tissue is so small that the measurement is always evaluated near the noise floor. In this respect, the measurements are expected to be greatly affected by noise contamination, imaging conditions, and analysis methods. It should also be noted that the evaluation of BBB leakage does not evaluate the entire glymphatic system, but only a part of the entire system.
Perivascular space volume
ophthalmopathy. Astronauts who spent 6 months on the International Space Station showed enlarged PVSs in the basal ganglia and white matter after their spaceflight. Furthermore, astronauts who developed spaceflightrelated neuro-ophthalmopathy had a more enlarged PVS in the white matter than those who did not develop the syndrome, indicating that long-term changes in gravity may affect the function of the glymphatic system.
Choroid plexus volume
brain, and regulation of CSF composition for homeostatic brain function have been identified.
Diffusion-based methods other than ALPS method
Arterial spin labeling
Imaging for brain tissue kinetics
coupling was associated with the cognitive decline seen in patients with PD. Additionally, lower BOLD-CSF coupling in PD patients was associated with a thinner right entorhinal cortex.
Other tracer study methods
extracranial accumulation of tracer was in the nasal turbinates. In patients with
Consideration for the Methodology of DTI-ALPS
Placement of ROI
Reproducibility of ALPS method

Variation of ALPS method
and 3-axis DWI showed a good correlation. This suggests the possibility of using the DWI-ALPS method with triaxial MPG.
examinations.
Controversy in DTI-ALPS Method
Conclusion
as a common term in this research area. It would be correct to describe the ALPS-index only as high or low, increased or decreased, and whether it reflects the glymphatic system or not should be considered as a subject for discussion. In other words, if a decrease in ALPS-index is observed, the title of the paper should say “decrease in ALPS-index” and not “glymphatic dysfunction” directly at least in the title of the paper. With regard to ALPS method, Professor Iliff mentioned that “Changes in the measure are seen under conditions where glymphatic function are impaired – so while we don’t have a strong handle on the exact nature of the signal it seems to work at some level” (personal communication), and the author agree with his opinion.
Conflicts of Interest
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Department of Innovative Biomedical Visualization (iBMV), Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
Department of Radiology, Nagoya University, Nagoya, Aichi, Japan
Department of Radiology, Aichi Medical University, Nagakute, Aichi, Japan
*Corresponding author: Department of Innovative Biomedical Visualization (iBMV), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. Phone: +81-52-744-2328, Fax: +81-52-744-2335, E-mail: ttaoka@med.nagoya-u.ac.jpThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives International License.
©2024 Japanese Society for Magnetic Resonance in Medicine
Received: December 25, 2023 | Accepted: February 22, 2024
