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磁気共鳴法を用いたイヌの変性性脊髄症の新規診断手法に関する研究

内藤, 瑛治 岐阜大学

2022.03.25

概要

イヌの変性性脊髄症(DN)は高齢で発症する慢性進行性の致死性神経変性疾患であり、本邦ではペンブローク・ウェルシュ・コーギー(PlC）での発症が多い。PICのDN発症大はスーパーオキンドジスムターゼ1(SODI)遺伝子の変異を変異型ホモ接合体で有するため、変異型S0D1タンパクがDNの病態に深く関与していると考えられている。しかし、SOD/遺伝子の変異型ホモ接合体であってもDNを発症しない個体が存在するため，遺伝子検査だけでDNを診断することはできない。現在，DNの確定診断には脊髄の病理組織学的検査が必要であり、生前診断法は確立されていない。DN発症初期からの病理組織学的特徴として，脊髄白質における髄鞘と軸索の脱落が認められる。さらに、神経根の髄鞘と軸索の脱落や、骨格筋の萎縮と筋線維の変性も認められる。これらに対し，磁気共鳴画像（MRI)の原理を応用した特殊な診断手法が有用である可能性が考えられる。水分子の動きを捉え，脊髄組織の傷害の程度を定量する拡散テンソル画像（DrI)や，水の信号を選択的に励起することで空間分解能を高めることにより，神経組織の描出能を向上させる水選択励起（WE）法はDNの育髄や神経根の解析に利用されている。また、MRI装置は骨格筋の評価にも有用であり，ヒトのSOD7遺伝子変異関連疾患である筋萎縮性側索硬化症（ALs）では，MRIを用いて傍脊柱筋を定性的に評価することで類似疾患との鑑別が可能と報告されている。本研究では，DNに特徴的な病理組織学的変化に着目した，MRIを利用した生前診断手法の開発を行なった。

第1章ではDMにおける脊髄病変をDTTによって検出することを目的に研究を行った。DN発症PIC(DN群）8頭，疾患対照群13頭および対照群6頭の胸腰髄におけるDrIデータを取得し，第8胸髄から第3腰髄の各椎間板レベルの脊髄および第8胸髄から第3腰髄の胸腰部脊髄領域（T8-L3領域）の神経線維束における見かけの拡散係数（ADC）および異方性比率(FA）を定量値として算出した。DN群におけるT8-L3領域のADC値およびFA値は、いずれも疾患対照群および対照群と比較すると有意に低値を示した。さらに，T8-L3領域のADC値はDMの発症期間と負の相関関係を示した。以上のことから、DM発症犬における脊髄変性はDTIにより非侵襲的に定量化が可能でき，生前診断手法として確立できると考えられた。

第2章ではVE法を用いた背根神経節（DRG）の体積定量手法の確立およびDNにおけるDRG体積測定の有用性を評価することを目的に研究を行った。DN群8頭、疾患対照群24頭および対照群8頭の胸腰部におけるWE画像を取得した。第8胸椎から第2腰椎レベルにおけるDRGの体積は，いずれもDN群が疾患対照群および対照群よりも有意に低値を示した。
さらに，DN群における第8胸椎から第2腰椎までのDRG体積の平均値は，疾患対照群および対照群と比較すると有意に低値であった。一方，DRG体積の平均値はDNの発症期間との相関関係を認めなかった。以上の結果より，DM発症犬におけるDRGの萎縮はSE法により描出することができ，病初期からの萎縮を認めるものの，病期の診断には適さないことが明らかとなった。

第3章ではDN発症早期，DM発症後期および対照犬を用いて「1強調画像における傍脊柱筋群の信号強度および筋断面積を評価することを目的とした。DN発症早期（早期DN群）9頭，発症後期（後期DN群）4頭，対照群6頭を用いて，第9胸椎から第3腰椎レベルの傍脊柱筋群における信号強度および断面積を比較した。早期DN群における第9胸椎の多裂筋の信号強度および断面積は対照群と比較して増加していたことから，第9胸椎の多裂筋の変性がT1強調画像上で描出できた可能性がある。また，傍脊柱筋群について後期DN群は早期D群と比較して信号強度は有意に高値を示し、断面積は有意に低値を示した。この結果は，DN臨床ステージが進行すると，筋内への脂肪浸潤による信号強度の増加および廃用性筋萎縮による筋体積の減少が生じたためと考えられた。T1強調画像における傍脊椎筋群の信号強度および断面積の解析は、DMの生前診断および病期の進行度の評価手法として期待できる。

本研究では，WRI装置を用いた解析によりDI発症犬における病理組織学的特徴を非侵襲的に検出でき，DNの生前診断の一助となることが示された。さらに，MRI装置を用いた解析はDの進行状況を把握することができるため，治療のモニタリングマーカーとしての有用性が期待できる。

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