兽研摘要
目的
超声造影（CEUS）是一种无创且相对安全的评估眼部灌注的成像技术，在人类肿瘤学中对肿瘤定性具有高灵敏度和特异度，而其应用于犬猫患病眼部的报道有限。本研究旨在描述犬猫眼眶及眼内病变的CEUS特征，以评估其在检测和定性各种病变中的诊断价值。
研究动物
回顾性评估了30只动物（24只犬、6只猫）的CEUS检查。
方法
在B型超声检查后，使用六氟化硫进行CEUS检查。病变被归类为以下各组之一：眼眶肿瘤性病变、眼眶炎性病变、眼内肿瘤性病变、眼内炎性病变和视网膜脱离。评估定性灌注参数、造影强度、增强模式、灌注类型以及流入和流出时间。
结果
CEUS检测到眼眶及眼内病变中的血管化，具有不同的增强特征。所有视网膜脱离病例均观察到持续性血管化。在眼眶及眼内肿瘤性病变中，CEUS改善了病变定位、与周围组织相互作用的评估以及组织灌注评估。对于脓肿、肌炎和脂肪炎等炎性病变，CEUS相较于B型超声的附加诊断价值有限。
结论
研究结果表明，CEUS可识别多种眼眶及眼内病变，并为B型超声提供附加诊断信息，特别是在评估肿瘤性病变和视网膜脱离方面。CEUS有潜力增强眼科超声检查以鉴别特定病变。需要前瞻性研究进一步评估其临床应用。
关键词：犬、CEUS、超声造影、猫、病变、视网膜脱离
1. 引言
眼部病变的成功治疗取决于准确诊断。当眼介质中存在混浊时，无论是炎性、退行性还是其他来源，都可能使眼科检查复杂化，从而限制针对性诊断[1,2,3]。为进一步评估，B型超声是最常用的无创、经济有效的方法，可显示眼部和眼眶结构，从而更精确地评估现有病变[4,5,6,7]。然而，其诊断价值因疾病而异[8]。高分辨率超声和超声生物显微镜可提供前节的详细信息，但不太适合评估后节和眼周区域[7,9]。彩色和能量多普勒成像易受眼球运动伪影的影响，使判读更加困难[10]。此外，低速血流小血管的血流显示仍然具有挑战性，因为整体组织运动可能超过毛细血管血流[8,11,12]。
超声造影（CEUS）在兽医和人类医学中均已获得诊断重要性。它是一种无创技术，可帮助犬猫鉴别视网膜脱离与玻璃体膜[10]。与多普勒方法相比，CEUS可显示犬、猫和人类更小的血管[10,12,13,14]。Blohm等[15]证明，对侧眼可作为可靠的体内参考，并且在无眼部病变的比格犬中，应在给予六氟化硫后60秒内评估血管增强。
在人类肿瘤学中，CEUS是肿瘤定性和治疗管理的有用诊断技术[16,17]。它在眼眶占位性病变的诊断中显示出高灵敏度和特异度，并可能有助于鉴别眼内肿瘤的良恶性[18,19]。在对化疗有反应的患者中，已观察到肿瘤血供逐渐减少[16,17]。仅有少数研究报道了CEUS在患有肿瘤性病变的犬猫眼部中的应用[20,21]。Andreani等[20]推测CEUS在检测眼内肿块内血流方面优于彩色多普勒。Quarta等[21]报道了正常和肿瘤性猫葡萄膜中的造影增强，疑似肿瘤眼的主观血管化增加。
总之，这些发现支持CEUS作为一种有前景、无创且敏感的评估眼部病变血流的方法[10,12,15,20,21]。
本回顾性研究的目的是描述犬猫眼眶及眼内病变的CEUS表现和灌注特征。我们假设CEUS为传统B型超声提供附加诊断价值。
2. 材料与方法
2.1. 动物
本回顾性研究纳入2016年1月至2017年7月在维也纳兽医大学接受CEUS检查并记录于电子病历系统中的患有眼眶和/或眼内病变的犬和猫。纳入标准为完整的眼科检查、传统B型超声和CEUS。
患者数据及病史，包括患者在维也纳兽医大学眼科单元初次就诊时的检查结果，均从数据库中检索获得。收集的信息包括年龄、性别、体重、品种、眼科及超声检查结果以及诊断后的干预措施。在可获得的情况下，还收集了额外的影像学检查结果（X线片、计算机断层扫描[CT]、磁共振成像[MRI]）以及细菌学、病理学和细胞学结果。随访检查结果、疾病进展及并发疾病亦被纳入考虑。对于无明确诊断的病例，最终诊断基于所有可用标准确定，特别侧重于诊断性手术操作的结果及治疗反应。
2.2. B型及超声造影
所有超声造影检查前均先行B型超声检查。检查使用12–5 MHz线阵探头或采用PureWave晶体技术的xMATRIX扇阵探头，工作频率范围为6–1 MHz（IU22；Philips，Bothell，WA）。涂抹耦合剂以确保探头与眼睑之间的声学耦合。超声检查在盐酸奥布卡因滴眼液（Novain；Agepha，Vienna，Austria）表面麻醉下经眼睑进行，动物根据配合程度保持清醒或镇静状态。对于计划手术的患者，检查在全身麻醉下进行。
造影成像使用六氟化硫（SonoVue；Bracco，Milan，Italy），按照Blohm等人[15]描述的技术进行，采用经眼睑而非经角膜的探头放置方式。除一只动物（D5——外侧隐静脉）外，所有动物均经头静脉注射造影剂。16例患者（11只犬、5只猫）接受0.03 mL/kg的剂量[22,23]，6例患者（5只犬、1只猫）接受每只动物0.5 mL的剂量，8只犬接受按体重确定的每只动物1 mL剂量（< 20 kg：0.5 mL，> 20 kg：1 mL），参照O'Brien等人[23,24]的方法。所有检查的机械指数（MI）范围为0.05至0.10。
每次造影研究中，在注射造影剂后立即录制垂直或水平扫描的2分钟视频片段并进行数字化存储（dicomPACS View Version 6.0.2，457，Bodmin，UK；Oehm und Rehbein，Rostock，Germany）。所有操作均由同一位放射科医师（K.M.H.）和眼科医师（K.O.B.）完成，二者对眼科检查结果均非盲态。
病变分为五组：眶内肿瘤性病变、眶内炎性病变、眼内肿瘤性病变、眼内炎性病变及视网膜脱离。对每种病变类型进行造影强度（CI：强、中等、低、可变）和增强模式（EP：不均匀、均匀、环状）的定性分析。对于孤立性病变，超声造影评估包括病变可见性、灌注类型（离心性、向心性、弥漫性、紊乱性、环状）以及相对于周围组织的洗入（WI）、洗出（WO）和造影剂滞留时间，只要这些特征可从现有记录中评估。不同灌注类型的定义如下：离心性灌注定义为增强始于病变中心部分并向周边进展，而向心性灌注定义为增强始于周边并向中心进展。弥漫性灌注的特征为增强累及整个病变，整个病理区域均显示增强，且无明确可识别的方向性进展。环状灌注定义为主要沿病变外缘的周边增强，中心灌注缺失或显著减低。当灌注无法一致地归入上述任一模式且无法识别出主要或可重复的灌注模式时，归类为紊乱性灌注。
增强动力学的定性描述基于从记录的超声造影检查中获得的测量值，包括WI和WO。采用以下研究特定定义：快速洗入为静脉注射造影剂（ICA）后≤ 10 s；缓慢洗入为ICA后> 10 s；快速洗出为ICA后≤ 60 s；延迟洗出为ICA后> 60 s。对于有多发病变的眼，分析与该临床表现最相关的病变。所有超声检查均由三位作者（J.I.O.、K.M.H.、K.O.B.）进行回顾性审阅。
3. 结果
30只动物（36只眼）符合纳入标准，包括24只犬（29只眼）和6只猫（7只眼），部分动物表现为双侧病变。信号特征、诊断及受累眼记录于表1。大多数检查在清醒动物中进行（25只动物）。3例患者需要镇静，2只动物在全身麻醉下接受检查。25只动物使用12–5 MHz线阵探头，5只动物使用采用PureWave晶体技术的xMATRIX扇阵探头（6–1 MHz）。
表1.
纳入研究的犬和猫的信号特征、诊断及受累眼。
缩写：C，猫；CKCS，骑士查理王小猎犬；D，犬；kg，千克；OD，右眼；OS，左眼；OU，双眼。
病变的左右侧对比见表2。
表2。
病变特征。
注：快速流入≤10秒（注射对比剂后）；缓慢流入>10秒（注射对比剂后）；快速流出≤60秒（注射对比剂后）；延迟流出>60秒（注射对比剂后）。
缩写：C，猫；D，犬；FROMS，猫限制性眶肌纤维母细胞肉瘤；ICA，静脉对比剂。
3.1. 眶内肿瘤性病变
两只犬（2眼）和两只猫（2眼）表现为眶内肿瘤性病变。所有动物的组织病理学检查均确诊。
瞬膜腺癌在B型超声上表现为2.2×2.5 cm的低回声圆形肿块，将眼球向背侧和颞侧推移。在超声造影上可见快速流入。周围组织先增强，随后病变表面可见个别血管，呈不均匀向心性增强和强对比强度。流出延迟且从中心开始。周边血管可见时间较长，伴有部分间歇性向心性增强。
犬眶内脑膜瘤在B型超声上表现为2.1×2.4 cm的不均匀、低回声至强回声实性肿块。在超声造影上，首先观察到肿块内缓慢流入，随后邻近组织流入。微泡呈离心模式循环，随后出现中等对比强度和不均匀增强，以中心为主。邻近组织的对比强度低于肿块。周围组织观察到快速流出，随后肿块流出。
猫限制性眶肌纤维母细胞肉瘤（FROMS）表现为不均匀强回声，伴有眼周间隙占位效应，压迫眼球但无明显眼球突出。注射对比剂后，肿块无法与周围软组织清晰区分。快速摄取对比剂后，眶间隙显示强对比强度，整个受累眶间隙呈不均匀增强模式。灌注类型为弥漫性。对比剂在病理组织中持续时间长于邻近结构，并显示快速流出。
恶性淋巴瘤位于球后，在B型超声上表现为2.4×1.73 cm的不规则低回声肿块，将眼球向背侧和颞侧推移。超声造影显示快速离心性增强，随后出现强对比强度，肿块呈均匀增强模式（图1）。短暂滞留后，流出从肿块内部开始，随后周围组织流出。
[图表内容请查看原文]
3.2. 眶内炎性病变
12只犬（14眼）和三只猫（4眼）诊断为眶内炎性病变。病变包括5例脓肿（5眼）、2例脂肪炎（3眼）、3例外眼肌炎（5眼）和3例并发脂肪炎和肌炎（3眼）。还记录到1例不确定病例（肌炎与脂肪炎，1眼）和1例单侧瞬膜淋巴组织细胞性炎症（1眼）。所有病例均经手术探查确诊脓肿。9只动物中有7只（9/12眼）根据治疗反应推测为肌炎和/或脂肪炎。在随访期间，各种全身治疗方案（包括非甾体或甾体抗炎治疗，伴或不伴额外广谱抗生素治疗）下观察到临床改善和病变消退。瞬膜淋巴组织细胞性炎症经组织病理学确诊。
脓肿（5眼）在B型超声上主要表现为低回声病变，内含一些强回声颗粒（1眼，图2），至无回声圆形病变（2眼）或部分分隔病变（1眼）。在两例（2眼）中，常规超声未能检测到手术确诊的脓肿。在这些病例中，球后区域表现为不均匀强回声。
[图表内容请查看原文]
注射对比剂后，脓肿显示缓慢流入和延迟流出（3眼）。1例病变表现为无血管腔，周围组织摄取对比剂（边缘增强，1眼）。当脓肿包膜及其内容物均增强时，脓肿内部对比强度低于包膜（2眼）。
在两例B型超声未显示的病例中，超声造影也未能显示脓肿特异性增强特征。相反，球后间隙表现为中等（1眼）至强（1眼）对比强度，呈不均匀增强模式（2眼）。
外眼肌炎在常规超声上表现为球后肌肉低回声增厚（8眼）和周围组织不均匀（4眼）。肌炎伴（5眼）或不伴（5眼）并发脂肪炎。
脂肪炎在B型超声上表现为球后脂肪强回声和不均匀（5眼），其中2眼伴有球后水肿。超声造影显示增厚肌肉和受累脂肪组织主要呈不均匀增强模式，流入、流出和对比强度可变（12眼）。1眼脂肪炎进一步表现为球后脂肪内高对比剂摄取。另1例（1眼）眼肌内可见线状对比剂充盈缺损。双侧病变显示相同的增强模式。
瞬膜淋巴组织细胞性炎症（炎性假瘤）在超声上表现为一个实性、均匀、眼球周、鼻侧的团块，压迫并使眼球及邻近组织移位。在CEUS上，该病变表现为快速WI，呈向心性灌注类型和均匀增强模式，对比剂强度向中心逐渐降低。整体CI强。WO快速（图3）。
[图表内容请查看原文]
3.3. 眼内肿瘤性病变
在三只犬（3只眼）中发现了眼内肿瘤性病变。组织病理学证实两只犬（2只眼）为黑色素瘤，一只犬（1只眼）为神经外胚层来源的肿瘤。
黑色素瘤在B型超声上表现为：一只眼为起源于虹膜、延伸至睫状体、向后进入脉络膜并进入玻璃体的1.45 × 0.63 cm圆形高回声团块；另一只眼为内侧虹膜内8.15 × 4.3 mm的圆形低回声团块。在CEUS上，两个黑色素瘤均表现为快速WI，病变增强略早于周围组织。一个病变表现为离心性灌注类型，随后与周围组织呈等增强。在另一个病变中，血管从巩膜-脉络膜视网膜缘延伸进入肿瘤。两个病变均表现为整体强CI和均匀增强模式。一只眼的WO从中心开始，而另一只眼的WO从瞳孔区开始并穿过团块向睫状体进展。两个病变的WO均快速（图4）。
[图表内容请查看原文]
神经外胚层肿瘤在B型超声上表现为内侧虹膜上6 mm的高回声团块，从鼻侧延伸至颞侧。给予对比剂后，缓慢WI主要位于病变内，细小血管呈离心性增强类型，中心对比剂强度更高。该圆形团块表现为中等CI和均匀增强模式。延迟WO后，对比剂强度从外周向中心降低。
3.4. 眼内炎性病变
在两只犬（3只眼）和一只猫（1只眼）中发现了眼内炎性病变。其中包括一例经病理学证实的眼内炎（1只眼）和两例经抗炎治疗有效证实的葡萄膜炎（3只眼）。
眼内炎由B型超声上可见的1.5 cm长高回声线状异物引起。其他发现包括虹膜高回声增厚以及前房和玻璃体内回声性颗粒。在CEUS上，受累区域（巩膜-脉络膜视网膜缘、前葡萄膜）表现为快速WI，中等CI，巩膜-脉络膜视网膜区域呈均匀增强模式。异物或眼内颗粒内未见对比剂增强。WO延迟。
葡萄膜炎在常规超声上表现为高回声增厚，尤其是脉络膜。在CEUS上，病变表现为快速WI（图5）。微泡从巩膜-脉络膜视网膜区域（3只眼）均匀扩散至前葡萄膜，CI从中等（2只眼）到强（1只眼）不等。WO方向相反，从吻侧向尾侧，整体延迟。在双侧葡萄膜炎病例中，增强模式相同。
[图表内容请查看原文]
3.5. 视网膜脱离
根据临床表现和眼科检查（7/7只眼）在五只犬（7只眼）中诊断了视网膜脱离，并经病理学在2/7只眼中证实。并发发现包括眼内出血（6只眼）和青光眼（1只眼）。
在B型超声上，视网膜脱离表现为从眼底延伸进入玻璃体的凸面或V形高回声结构。在六只眼中，并存的出血产生了与脱离视网膜回声性相似的高回声结构，仅凭B型超声无法明确诊断。在CEUS上，视网膜灌注始终可被识别（7/7只眼），有助于与其余未增强的高回声结构（出血）相鉴别。在3/7只眼中，微泡沿脱离的视网膜呈现振荡运动（图6）。在双侧视网膜脱离（2只犬，4只眼）中，一例视网膜呈等回声，另一例显示不同程度的CI。在受青光眼影响的眼中，视网膜CI降低且以不均匀为主。
[图表内容请查看原文]
4. 讨论
本研究表明，CEUS可有效显示眶内和眼内病变，并揭示不同的增强模式，尤其是对眼内和眼外肿瘤性病变。此外，CEUS在视网膜脱离病例中始终能检测到持续的视网膜灌注。
在兽医眼科中，CEUS是一种无创、相对安全的影像学技术，用于评估正常眼和患病眼的灌注情况[10，12，15，20，21]。与以往聚焦于单一物种或品种的研究不同，本病例系列纳入了不同年龄、性别和品种的犬和猫的CEUS检查，从而反映了常规临床环境。值得注意的是，大多数CEUS检查是在清醒动物中进行的，表明通常不需要镇静。这一观察结果与Blohm等人[15]的发现一致，他们定量分析了10只清醒比格犬的眼内和眼外灌注，并推测即使在局部麻醉下的疼痛状态下，CEUS也可能具有良好的耐受性[15]。本研究结果支持这一假设，因为纳入的若干患者表现出眼痛的临床体征，但仍能耐受该操作。
仅有少数研究报道了CEUS在患病犬眼和猫眼中的应用[10，20，21]。在视网膜脱离中，造影增强提示视网膜有血管化，而玻璃体膜保持无血管[10]。在本研究中，CEUS通过显示持续的视网膜血管化，使脱离的视网膜与玻璃体内的强回声物质得以区分，从而有助于视网膜脱离的诊断。这一发现与Labruyere等人[10]的兽医研究和Sconfienza等人[16]的人类研究一致。此外，在一些眼中观察到微泡沿视网膜的双向运动，提示动脉和静脉血流均持续存在[10]。在因全身性疾病导致双侧视网膜脱离的病例中，CEUS结果显示双眼的增强模式相同。然而，合并青光眼的眼主观上显示灌注减少，最可能反映了眼内压升高对血管直径和血流的影响，表现为CEUS上CI降低[25]。
在犬和猫患者中，4周内或更短时间内视网膜复位与更良好的预后相关[10，26]。CEUS是评估视网膜活力的可靠方法，即使脱离持续时间未知，也可能有助于预测玻璃体视网膜手术成功或失败的可能性[10]。
在犬眼和猫眼肿瘤病例中，CEUS被认为在检测眼内肿物内血流和识别疑似肿瘤中血管化增加方面优于彩色多普勒和能量多普勒超声检查[20，21]。
与既往报道[19，27]相似，本系列中的黑色素瘤病例表现为向心性增强、均匀模式、强CI，且病灶内造影剂滞留时间短于周围组织。与既往研究[27]不同，这些病灶的造影剂摄取略早于周围组织。各研究间的流入和WO特征不一致；然而，与本研究的病例相似，总体趋势为快速WI和快速WO[18，19]。另一篇文献[16]强调了CEUS在评估脉络膜黑色素瘤方面的潜力，强调其能够显示黑色素瘤典型的显著血管化并将其与脉络膜痣区分开来，以及通过检测肿瘤血流的逐渐下降来监测放疗后治疗反应的效用。在本病例系列中，评估了两例黑色素瘤，尽管位置不同，但表现出 consistent 的增强模式。虽然未纳入猫弥漫性虹膜黑色素瘤病例，但CEUS在这一诊断具有挑战性的疾病中的应用值得进一步研究。
在人类眼科中，CEUS被认为是诊断眶内占位性病变的合适影像学技术[19]。对于眼内肿瘤的良恶性鉴别，据报道灵敏度为98.3%，特异度为100%[18]。恶性肿瘤（如脉络膜黑色素瘤、脉络膜转移瘤和视网膜母细胞瘤）通常以丰富的血供为特征，CEUS表现为快速WI、达峰时间短、强高回声信号和快速WO[19]。这种行为反映了肿瘤诱导的血管生成，导致大量异常的动脉和静脉血管，血容量高。相比之下，良性病变以薄壁静脉血管内低流速血流为特征，这解释了其在CEUS上独特的增强模式。良性病变如血管瘤、黑色素细胞瘤、钙化和假瘤，通常表现为快速WI伴缓慢WO[18，19]。
在我们的病例系列中，犬假瘤表现为快速均匀的向心性增强，中央区域的对比强度低于外周，并出现快速廓清。由于我们尽可能聚焦于病灶灌注的成像，成像窗口仅包含假瘤而未纳入相邻参考组织，因此无法将WI和WO特征与周围组织进行直接比较。中央对比强度减低可能反映病灶内中央坏死区域。这一解释得到既往研究结果的支持，其中“充盈缺损”被认为是中央坏死的可能影像学相关表现。值得注意的是，即使在组织病理学证实存在中央坏死的病例中，此类影像学特征也未必总被明确强调，这凸显了该发现在CEUS上的细微性[19]。
总体而言，炎性假瘤中已有类似的CEUS特征报道，包括快速WI后呈均匀增强，以及与我们的病例不同，表现为缓慢WO且病灶增强程度超过周围组织。其研究中的组织病理学结果显示散在坏死和慢性炎性细胞浸润[19]。
相比之下，本假瘤病例与一例诊断为腺癌的患者位于相同解剖部位（瞬膜），并在常规超声上表现为相似的占位效应。尽管在位置和超声表现上存在这些相似之处，但 underlying 病理不同，一为肿瘤性，一为炎性。值得注意的是，两个病灶的CEUS对比行为不同，且两种诊断均经组织病理学证实。淋巴细胞组织细胞性假瘤主要表现为均匀的向心性增强模式，对比强度向中心逐渐减低，无明显病灶内异质性或明确的早期局灶性血管不规则。此外，病灶表现为快速WI后快速WO。
相比之下，瞬膜腺癌表现为更不均匀的增强行为，周围组织先增强，随后早期显示浅表肿瘤血管。病灶内增强不规则且呈向心性，随后为短暂的峰值期和较早的中央廓清。外周血管可见时间更长，伴间歇性向心性充盈。腺癌也表现为快速WI，但与假瘤相反，表现为延迟WO。总体而言，本病例的CEUS表现仅部分符合人类医学中描述的区别特征。虽然假瘤和腺癌均观察到快速WI，但WO特征与人类常见描述模式不同，假瘤为快速WO，腺癌为延迟WO。因此，根据人类医学中描述的标准，仅凭WI和WO特征在这两个病例中无法区分炎性疾病与肿瘤性疾病[18,19]。相反，观察到的增强模式和血管结构差异可能为鉴别提供额外信息。
若干因素可能限制与上述人类研究的直接比较。用于将WI和WO归类为快速、缓慢或延迟的定义和时间阈值在不同研究间可能存在差异，且人类与兽医患者之间肿瘤生物学和血管结构的差异可能影响对比增强行为。此外，现有研究描述的是炎性假瘤的CEUS特征，而腺癌的具体CEUS特征尚未见报道[18,19]。此外，一项研究[18]使用定量时间-强度曲线分析评估对比动力学，而本研究依赖定性评估，这可能影响了WI和WO的分类。鉴于这些局限性和病例数较少，这些观察结果应谨慎解读，并需在更大规模的前瞻性研究中予以证实。
在人类医学中，视神经淋巴瘤和脑膜瘤因其显著的血管化被认为特别适合CEUS诊断[16]。在本研究中，两种肿瘤均通过CEUS显像，提供了关于其增强特征的额外信息。淋巴瘤病例中的离心性增强模式与犬和猫纵隔淋巴瘤中报道的相似[28]。据推测，这反映了这些肿瘤类似淋巴结的血管结构，其灌注由中央进入的门部血管维持[28,29]。虽然脑膜瘤因其显著的血管化被认为是适合CEUS的病灶，但其具体CEUS特征仍未被描述，凸显了对这一临床相关肿瘤进行进一步研究的必要性。
炎性病变中强烈的CEUS增强主要归因于炎性充血和血管扩张，导致局部灌注增加。然而，并非所有炎性病变均表现出一致的增强[23]。迄今为止，尚无研究描述CEUS在眼眶或眼内炎性病变中的应用。在本研究中，炎性病变中观察到不同程度的造影强度，尽管作者注意到快速WI和延迟WO倾向于更强的增强。这与活动性炎症组织中预期的充血反应一致。增强程度的变异性可能与潜在病理生理阶段和炎症严重程度的差异以及受累组织类型有关。伴有明显血管扩张的急性炎症过程可能表现出更强且更均匀的增强，而更慢性或活动性较低的炎症状态可能因血管重塑或组织损伤而表现出减弱或不均匀的增强模式[23]。
观察到的脓肿囊壁增强而脓肿内容物无增强与既往对比增强MRI的研究结果一致[30,31]。Dennis[11]报道了一例眼部脓肿，常规超声最初误诊为肿瘤，通过MRI上的囊壁增强得以正确识别。本系列中有两例显示脓肿内有一定程度的造影剂摄取，尽管囊壁通常表现为更强的周边增强。病灶内造影增强可能归因于脓肿内血管化的分隔[32]。需要注意的是，纳入病例中有两个脓肿在B型超声和CEUS上均无法检出，这表明对于眼眶脓肿，CEUS相对于常规B型超声的优势应谨慎解读。
关于肌炎和脂肪组织炎，Fischer等[31]使用对比增强MRI报道了异常增强模式和肿胀。在人类医学中，CEUS已被证明在诊断肌炎方面比常规超声更有效，因为它能够量化急性病例中炎症诱导的肌肉过度灌注[33,34]。然而，在本研究中，未观察到一致的造影增强特征，提示CEUS相对于B型超声对这些病变的额外诊断价值仍存疑问。
本病例系列的局限性包括其回顾性设计以及操作者对疑似诊断未设盲，这可能引入潜在偏倚。此外，使用了不同的造影剂剂量和超声探头。然而，本研究中使用的剂量和探头均提供了满意的造影增强效果。大多数动物在无镇静状态下接受CEUS，但在镇静或麻醉病例中，心血管变化可能影响灌注。
样本量有限，无法进行物种特异性分析，这在未来评估猫弥漫性虹膜黑色素瘤或FROMS等疾病的研究中可能具有价值。在某些病例中，无法获得组织病理学确认，诊断仅基于治疗反应。此外，许多动物同时存在多种眼部病变，这可能影响了CEUS的发现。
最后，未进行时间-强度曲线的定量分析，尽管Blohm等[15]已表明定性和定量结果可能存在差异。鉴于本研究的主要目的是描述CEUS的实际适用性，研究侧重于定性评估，并承认其固有的主观性。然而，本研究中报告的时间间隔（以秒为单位）应谨慎解读，因为未进行基于感兴趣区测量的正式定量时间-强度曲线分析。所提供的数值基于对记录的CEUS检查的观察性评估，应视为近似参考点而非精确的定量测量。因此，它们主要用于补充造影增强动力学的定性解读，并便于读者理解和病例间比较。
本研究利用CEUS对各种眼眶和眼内病变的灌注特征提供了初步见解。需要进一步研究来评估CEUS基于增强特征鉴别或诊断特定病变的潜力。
考虑到造影剂成本较高以及需要专用软件，CEUS相对于B型超声在评估脓肿、葡萄膜炎、眼内炎、肌炎和脂肪组织炎等炎性病变方面的额外诊断价值仍不确定。相比之下，CEUS一致地检测到视网膜脱离中的持续性视网膜灌注，并在肿瘤性病变中显示出独特的增强特征，可能反映了肿瘤血管特征，这可能在未来的临床应用中有助于鉴别肿瘤类型。
5. 结论
本病例系列强调了CEUS在可视化一系列眶内和眼内病变方面的实用性。在肿瘤性病变中，CEUS提供独特的增强特征，有助于精确定位，并展示组织灌注特征。这些特点可能有助于更准确地区分病变，支持CEUS作为传统眼科超声检查的有价值辅助手段的作用。
作者贡献
Janneke I. Ortner：概念构思、写作——初稿、数据管理、形式分析。Katharina M. Hittmair：概念构思、数据管理、监督、写作——审阅与编辑。Barbara Nell：概念构思、监督、写作——审阅与编辑。Klaas‐Ole Blohm：概念构思、写作——审阅与编辑、数据管理、监督。
披露
作者未使用人工智能生成稿件的任何部分。
伦理声明
动物主人已提供书面同意，同意为研究目的发表患者数据。
利益冲突
作者声明无利益冲突。
致谢
作者无需要报告的事项。开放获取资金由维也纳兽医大学提供。
数据可用性声明
支持本研究结果的数据可应通讯作者要求提供。由于隐私或伦理限制，数据不公开可用。
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ABSTRACT
Objective
Contrast‐enhanced ultrasonography (CEUS) is a noninvasive and relatively safe imaging technique to assess ocular perfusion, showing high sensitivity and specificity for tumor characterization in human oncology, while reports on its application in canine and feline diseased eyes are limited. This study aimed to describe the CEUS features of orbital and intraocular pathologies in dogs and cats in order to evaluate its diagnostic value in detecting and characterizing various lesions.
Animal Studied
CEUS examinations of 30 animals (24 dogs, 6 cats) were evaluated retrospectively.
Procedures
Following B‐mode ultrasonography, CEUS examinations utilizing sulfur hexafluoride were performed. Pathologies were categorized in one of the following groups: orbital neoplastic lesions, orbital inflammatory lesions, intraocular neoplastic lesions, intraocular inflammatory lesions and retinal detachment. Qualitative perfusion parameters, contrast intensity, enhancement pattern, perfusion type and time to wash‐in and wash‐out were evaluated.
Results
CEUS detected vascularization in orbital and intraocular pathologies, with variable enhancement characteristics. Persistent vascularization was observed in all cases of retinal detachment. In orbital and intraocular neoplastic lesions, CEUS improved lesion localization, assessment of interactions with surrounding tissues and tissue perfusion. For inflammatory pathologies such as abscesses, myositis, and steatitis, the additional diagnostic value of CEUS compared to B‐mode ultrasonography was limited.
Conclusion
Findings indicated that CEUS could identify a variety of orbital and intraocular pathologies and provided additional diagnostic information to B‐mode ultrasonography, particularly for assessing neoplastic lesions and retinal detachments. CEUS has the potential to enhance ophthalmic ultrasonography in differentiating specific pathologies. Prospective studies are warranted to further evaluate its clinical use.
Keywords: canine, CEUS, contrast‐enhanced ultrasonography, feline, lesions, retinal detachment
1. Introduction
Successful treatment of ocular pathologies depends on accurate diagnosis. When opacities are present in the ocular media, whether inflammatory, degenerative, or of other origin, they can complicate ophthalmic examination and thereby limit targeted diagnosis [ 1 , 2 , 3 ]. For further evaluation, B‐mode ultrasonography is most commonly performed as a noninvasive, cost‐effective method to visualize ocular and orbital structures, allowing more precise assessment of existing pathologies [ 4 , 5 , 6 , 7 ]. However, its diagnostic value varies among diseases [ 8 ]. High‐resolution ultrasonography and ultrasound biomicroscopy can provide detailed information on the anterior segment, but are less suitable for evaluating the posterior segment and periocular regions [ 7 , 9 ]. Color‐ and Power Doppler imaging are susceptible to artifacts caused by eye movements, making interpretation more difficult [ 10 ]. In addition, visualization of blood flow in small vessels with low blood flow velocities remains challenging, as overall tissue motion may exceed capillary blood flow [ 8 , 11 , 12 ].
Contrast‐enhanced ultrasonography (CEUS) has gained diagnostic importance in both veterinary and human medicine. It is a noninvasive technique that may aid in differentiating retinal detachment from vitreal membranes in dogs and cats [ 10 ]. In contrast to Doppler methods, CEUS allows visualization of smaller vessels in dogs, cats, and humans [ 10 , 12 , 13 , 14 ]. Blohm et al. [ 15 ] demonstrated that the contralateral eye can serve as a reliable in vivo reference and that vascular enhancement should be evaluated within 60 s after sulfur hexafluoride administration in beagles without ocular pathologies.
In human oncology, CEUS is a useful diagnostic technique for tumor characterization and therapeutic management [ 16 , 17 ]. It shows high sensitivity and specificity for the diagnosis of orbital space‐occupying lesions and may be beneficial in differentiating benign from malignant intraocular tumors [ 18 , 19 ]. In patients responding to chemotherapy, a gradual reduction in neoplastic blood supply has been observed [ 16 , 17 ]. Only a few studies have reported CEUS applications in canine and feline eyes with neoplastic lesions [ 20 , 21 ]. Andreani et al. [ 20 ] postulated CEUS to be superior to Color Doppler in detecting blood flow within intraocular masses. Quarta et al. [ 21 ] reported contrast enhancement in both normal and neoplastic feline uvea, with subjectively increased vascularization in eyes with suspected neoplasia.
Altogether, these findings support CEUS as a promising, noninvasive, and sensitive method to evaluate blood flow in ocular pathologies [ 10 , 12 , 15 , 20 , 21 ].
The aim of this retrospective study was to describe the CEUS appearance and perfusion characteristics of orbital and intraocular lesions in dogs and cats. We hypothesized that CEUS provides additional diagnostic value to conventional B‐mode ultrasonography.
2. Material and Methods
2.1. Animals
This retrospective study included dogs and cats with orbital and/or intraocular lesions that underwent CEUS at the University of Veterinary Medicine Vienna from January 2016 to July 2017 and were recorded in the electronic medical records system. Inclusion criteria were a complete ophthalmologic examination, conventional B‐mode ultrasonography, and CEUS.
Patient data and medical history including examination results from the initial presentation of the patients at the ophthalmology unit of the University of Veterinary Medicine Vienna were retrieved from the database. Collected information comprised age, sex, weight, breed, ophthalmic and ultrasonographic findings, and interventions following diagnosis. When available, additional imaging findings (radiographs, computed tomography [CT], magnetic resonance imaging [MRI]) as well as bacteriological, pathological, and cytological results were collected. Follow‐up examination results, disease progression and concurrent pathologies were also considered. In cases without a definitive diagnosis, the final diagnosis was determined based on all available criteria, with particular emphasis on the results of diagnostic‐surgical procedures and the therapeutic response.
2.2. B‐Mode and Contrast‐Enhanced Ultrasonography
All CEUS examinations were preceded by B‐mode ultrasonography. Examinations were performed using either a 12–5 MHz linear transducer or an xMATRIX sector transducer with PureWave crystal technology, operating within a frequency range of 6–1 MHz (IU22; Philips, Bothell, WA). A coupling gel was applied to ensure acoustic coupling between the transducer and the eyelids. Ultrasonography was performed transpalpebrally under topical anesthesia using oxybuprocaine hydrochloride ophthalmic drops (Novain; Agepha, Vienna, Austria), with animals either awake or sedated depending on their cooperation. In patients scheduled for surgery, examinations were conducted under general anesthesia.
Contrast imaging was performed using sulfur hexafluoride (SonoVue; Bracco, Milan, Italy) following the technique described by Blohm et al. [ 15 ] with a transpalpebral rather than transcorneal transducer placement. The contrast agent was administered via the cephalic vein in all animals except one (D5—V. saphena lateralis). Sixteen patients (11 dogs, 5 cats) received a dose of 0.03 mL/kg [ 22 , 23 ], six patients (5 dogs, 1 cat) received a dose of 0.5 mL per animal and eight dogs received a dose of 1 mL per animal determined by body weight (< 20 kg: 0.5 mL, > 20 kg: 1 mL) as per O'Brien et al. [ 23 , 24 ]. The mechanical index (MI) ranged from 0.05 to 0.10 for all examinations.
During each contrast study, a 2‐min video clip of either the vertical or horizontal scan was recorded immediately after contrast administration and digitally stored (dicomPACS View Version 6.0.2, 457, Bodmin, UK; Oehm und Rehbein, Rostock, Germany). All procedures were performed by the same radiologist (K.M.H.) and ophthalmologist (K.O.B.), who were not blinded to the ophthalmologic findings.
Pathologies were categorized into five groups: orbital neoplastic lesion, orbital inflammatory lesion, intraocular neoplastic lesion, intraocular inflammatory lesion, and retinal detachment. Contrast intensity (CI: strong, moderate, low, variable) and enhancement pattern (EP: heterogeneous, homogeneous, rim) were qualitatively analyzed for each lesion type. For solitary lesions, CEUS evaluation included lesion visibility, perfusion type (centrifugal, centripetal, diffuse, chaotic, rim) and the timing of wash‐in (WI), wash‐out (WO) and contrast retention relative to surrounding tissue whenever these features were assessable from the available recordings. The different perfusion types were defined as follows: centrifugal perfusion was defined as enhancement originating in the central portion of the lesion and progressing toward the periphery, whereas centripetal perfusion was defined as enhancement beginning at the periphery and progressing toward the center. Diffuse perfusion was characterized by enhancement involving the entire lesion, with the whole pathological area showing enhancement and without a clearly identifiable directional progression. Rim perfusion was defined as predominantly peripheral enhancement along the outer margin of the lesion, with absent or markedly reduced central perfusion. Perfusion was classified as chaotic when it could not be consistently assigned to any of the aforementioned patterns and no predominant or reproducible perfusion pattern could be identified.
Qualitative descriptors of enhancement dynamics were based on measurements obtained from the recorded CEUS examinations, including WI and WO. The following study‐specific definitions were applied: rapid wash‐in ≤ 10 s after intravenous contrast administration (ICA); slow wash‐in > 10 s after ICA; rapid wash‐out ≤ 60 s after ICA; delayed wash‐out > 60 s after ICA. In eyes with multiple lesions, the pathology most relevant to the clinical presentation was analyzed. All ultrasonographic examinations were retrospectively reviewed by three authors (J.I.O., K.M.H., K.O.B.).
3. Results
Thirty animals (36 eyes) met the inclusion criteria, comprising 24 dogs (29 eyes) and six cats (7 eyes), with some animals presenting bilateral lesions. Signalment, diagnosis, and affected eye are documented in Table 1 . Most examinations were performed in conscious animals (25 animals). Sedation was necessary in three patients, and two animals were examined under general anesthesia. The 12–5 MHz linear transducer was used in 25 animals, while the xMATRIX sector transducer with PureWave crystal technology (6–1 MHz) was used in five animals.
TABLE 1.
Signalment, diagnosis and affected eye of dogs and cats included in the study.
Abbreviations: C, cat; CKCS, Cavalier King Charles Spaniel; D, dog; kg, kilogram; OD, oculus dexter; OS, oculus sinister; OU, oculus uterque.
A side to side comparison of the lesions is seen in Table 2 .
TABLE 2.
Lesion characteristics.
Note: Rapid wash‐in ≤ 10 s ICA; slow wash‐in > 10 s after ICA rapid wash‐out ≤ 60 s after ICA; delayed wash‐out > 60 s after ICA.
Abbreviations: C, cat; D, dog; FROMS, feline restrictive orbital myofibroblastic sarcoma; ICA, intravenous contrast agent.
3.1. Orbital Neoplastic Lesions
Two dogs (2 eyes) and two cats (2 eyes) exhibited orbital neoplastic lesions. Histopathology confirmed the diagnosis in all animals.
The nictitating membrane adenocarcinoma appeared on B‐Mode ultrasound as a 2.2 × 2.5 cm hypoechoic, round mass displacing the globe dorsally and temporally. On CEUS there was a rapid WI. The surrounding tissue enhanced first, followed by visualization of individual vessels on the lesion's surface, with heterogeneous centripetal enhancement and strong CI. The WO was delayed and began centrally. Peripheral vessels remained visible for a longer duration, with some intermittent centripetal enhancement.
Canine orbital meningioma appeared on B‐mode ultrasound as a 2.1 × 2.4 cm heterogeneous, hypoechoic to hyperechoic solid mass. On CEUS, a slow WI was first observed within the mass, followed by adjacent tissue. Microbubbles circulated in a centrifugal pattern with subsequent moderate CI and heterogeneous enhancement, predominantly central. Adjacent tissue showed lower CI compared to the mass. A rapid WO was observed in the surrounding tissue, followed by the mass.
Feline restrictive orbital myofibroblastic sarcoma (FROMS) appeared heterogeneously hyperechoic with a mass effect in the periocular space, compressing the globe without significant exophthalmos. After contrast administration, the mass could not be clearly delineated from surrounding soft tissue. Following rapid contrast uptake, the orbital space showed a strong CI and heterogeneous enhancement pattern throughout the affected orbital space. The perfusion type was diffuse. Contrast persisted longer in the pathological tissue than in adjacent structures and showed a rapid WO.
Malignant lymphoma was located retrobulbar on B‐mode ultrasound as a 2.4 × 1.73 cm irregular, hypoechoic mass displacing the globe dorsally and temporally. CEUS revealed rapid centrifugal enhancement, followed by a strong CI, and homogeneous enhancement pattern in the mass (Figure 1 ). After a short retention WO began within the mass, followed by the surrounding tissue.
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3.2. Orbital Inflammatory Lesions
Orbital inflammatory lesions were diagnosed in 12 dogs (14 eyes) and three cats (4 eyes). Lesions included five abscesses (5 eyes), two cases of steatitis (3 eyes), three cases of extraocular orbital myositis (5 eyes), and three cases of concurrent steatitis and myositis (3 eyes). One equivocal case (myositis versus steatitis 1 eye) and one patient with unilateral lymphohistiocytic inflammation of the nictitating membrane (1 eye) were also recorded. Abscesses were confirmed in all cases by surgical exploration. Myositis and/or steatitis were presumed in 7 of 9 animals (9/12 eyes) based on response to therapy. Clinical improvement and resolution of lesions were observed during follow‐up under various systemic treatment regimens, including nonsteroidal or steroidal anti‐inflammatory therapy, with or without additional broad‐spectrum antibiotic treatment. Lymphohistiocytic inflammation of the nictitating membrane was confirmed histopathologically.
Abscesses (5 eyes) appeared on B‐mode ultrasound as predominantly hypoechoic lesions containing some echogenic particles (1 eye, Figure 2 ) to anechoic rounded lesions (2 eyes) or partially septated lesions (1 eye). In two cases (2 eyes), conventional ultrasonography failed to detect surgically confirmed abscesses. In these cases, the retrobulbar region appeared heterogeneously hyperechoic.
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Following contrast administration, abscesses demonstrated slow contrast wash‐in with delayed wash‐out (3 eyes). One lesion was characterized as a non‐vascularized cavity with contrast uptake in the surrounding tissue (rim enhancement, 1 eye). When both the abscess capsule and its contents enhanced, the abscess interior exhibited lower contrast intensity compared to the capsule (2 eyes).
In the two cases not visualized by B‐mode ultrasonography, CEUS also failed to demonstrate abscess‐specific enhancement characteristics. Instead, the retrobulbar space exhibited moderate (1 eye) to strong (1 eye) CI with a heterogeneous enhancement pattern (2 eyes).
Extraocular orbital myositis was characterized on conventional ultrasound by hypoechoic thickening of the retrobulbar muscles (8 eyes) and heterogeneous surrounding tissue (4 eyes). Myositis was observed either with (5 eyes) or without (5 eyes) concurrent steatitis.
Steatitis was characterized on B‐mode ultrasound by hyperechoic and heterogeneous retrobulbar fat (5 eyes), with associated retrobulbar edema in two eyes. CEUS revealed a predominantly heterogeneous enhancement pattern with variable WI, WO, and CI in both thickened muscle and affected fat tissue (12 eyes). Steatitis was further characterized by high contrast uptake within the retrobulbar fat in one eye. In another case (1 eye), a linear contrast filling defect within the ocular muscles was noted. Bilateral lesions demonstrated identical enhancement patterns.
Lymphohistiocytic inflammation of the nictitating membrane (inflammatory pseudotumor) was visualized ultrasonographically as a solid, homogeneous, peribulbar, nasal mass compressing and displacing the globe and adjacent tissues. On CEUS, the lesion exhibited a rapid WI with a centripetal perfusion type and a homogeneous enhancement pattern with progressively decreasing contrast intensity toward the center. The overall CI was strong. The WO was rapid (Figure 3 ).
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3.3. Intraocular Neoplastic Lesions
Intraocular neoplastic lesions were identified in three dogs (3 eyes). Histopathology confirmed melanoma in two dogs (2 eyes) and neoplasia of neuroectodermal origin in one dog (1 eye).
Melanoma appeared on B‐mode ultrasound either as a 1.45 × 0.63 cm round, hyperechoic mass originating from the iris with extension over the ciliary body, caudally into the choroid, and into the vitreous body (1 eye), or as an 8.15 × 4.3 mm round, hypoechoic mass in the medial iris (1 eye). With CEUS, both melanomas demonstrated a rapid WI with a slightly earlier enhancement of the lesion than surrounding tissue. One lesion demonstrated a centrifugal perfusion type and subsequently appeared isoenhanced to the surrounding tissue. In the other lesion, vessels extended from the sclero‐chorioretinal rim into the neoplasm. Both lesions exhibited an overall strong CI and homogeneous enhancement pattern. Wash‐out initiated centrally in one eye, whereas in the other eye, it began in the pupillary area and progressed across the mass toward the ciliary body. The WO was rapid in both lesions (Figure 4 ).
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The neuroectodermal neoplasm appeared on B‐mode ultrasound as a 6 mm, hyperechoic mass on the medial iris, extending from nasal to temporal. After contrast administration, slow WI was predominantly intralesional, with fine vessels exhibiting a centrifugal enhancement type and more intense contrast centrally. The round mass presented with moderate CI and a homogeneous enhancement pattern. Following a delayed WO, contrast intensity decreased from the periphery toward the center.
3.4. Intraocular Inflammatory Lesions
Intraocular inflammatory lesions were seen in two dogs (3 eyes) and one cat (1 eye). These included one case of endophthalmitis (1 eye) confirmed by pathology and two cases of uveitis (3 eyes), confirmed by positive anti‐inflammatory therapeutic response.
Endophthalmitis was caused by a 1.5 cm long, hyperechoic linear foreign body visible on B‐mode ultrasonography. Additional findings included hyperechoic iris thickening and echogenic particles in the anterior chamber and vitreous. On CEUS, the affected regions (sclero‐chorioretinal rim, anterior uvea) showed rapid WI with moderate CI and a homogeneous enhancement pattern in the sclero‐chorioretinal region. No contrast enhancement was observed within the foreign body or the intraocular particles. The WO was delayed.
Uveitis appeared on conventional ultrasound as a hyperechoic thickening, particularly in the choroid. On CEUS, lesions demonstrated rapid WI (Figure 5 ). Microbubbles spread homogeneously from the sclero‐chorioretinal area (3 eyes) into the anterior uvea, with CI ranging from moderate (2 eyes) to strong (1 eye). The WO occurred in the opposite direction, from rostral to caudal and was overall delayed. In cases of bilateral uveitis, enhancement patterns were identical.
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3.5. Retinal Detachment
Retinal detachment was diagnosed in five dogs (7 eyes) based on clinical findings and ophthalmologic examination (7/7 eyes) and confirmed by pathology in 2/7 eyes. Concurrent findings included intraocular hemorrhage (6 eyes) and glaucoma (1 eye).
On B‐mode ultrasonography, retinal detachment appeared as a convex or V‐shaped hyperechoic structure extending from the ocular fundus into the vitreous. In six eyes, coexisting hemorrhage produced hyperechoic structures with similar echogenicity to detached retina, precluding definitive diagnosis on B‐mode alone. On CEUS, retinal perfusion was consistently identified (7/7 eyes), facilitating differentiation from remaining non‐enhanced hyperechoic structures (hemorrhage). In 3/7 eyes, microbubbles exhibited oscillating movement along the detached retina (Figure 6 ). In bilateral retinal detachments (2 dogs, 4 eyes), the retina appeared isointense in one case and showed variable CI in the other. In the eye affected by glaucoma, CI of the retina was reduced and predominantly heterogeneous.
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4. Discussion
This study demonstrated that CEUS effectively visualized orbital and intraocular lesions and revealed distinct enhancement patterns, particularly for intra‐ and extraocular neoplastic lesions. In addition, CEUS consistently detected persistent retinal perfusion in cases of retinal detachment.
In veterinary ophthalmology, CEUS is a noninvasive, relatively safe imaging technique to assess perfusion in both normal and diseased eyes [ 10 , 12 , 15 , 20 , 21 ]. Unlike previous studies focusing on single species or breeds, the present case series included CEUS examinations of dogs and cats of varying ages, sexes, and breeds, thereby reflecting routine clinical settings. Notably, most CEUS examinations were performed in awake animals, indicating that sedation is not routinely required. This observation aligns with the findings of Blohm et al. [ 15 ], who quantitatively analyzed intra‐ and extraocular perfusion in 10 awake beagles and hypothesized that CEUS may be well tolerated even in painful conditions under local anesthesia [ 15 ]. The present results support this assumption, as several included patients exhibited clinical signs of ocular pain yet tolerated the procedure.
There are only a few studies reporting the use of CEUS in diseased canine and feline eyes [ 10 , 20 , 21 ]. In retinal detachments, contrast enhancement indicates vascularized retina, whereas vitreal membranes remain avascular [ 10 ]. In the present study, CEUS enabled the differentiation of the detached retina from hyperechoic material within the vitreous body by demonstrating persistent retinal vascularization, thereby facilitating the diagnosis of retinal detachment. This finding is consistent with veterinary and human studies by Labruyere et al. [ 10 ] and Sconfienza et al. [ 16 ], respectively. In addition, bidirectional movement of microbubbles along the retina was observed in some eyes, suggesting persistence of both arterial and venous blood flow [ 10 ]. In cases of bilateral retinal detachment due to systemic disease, CEUS results showed identical enhancement patterns in both eyes. However, the eye with concurrent glaucoma demonstrated subjectively reduced perfusion, most likely reflecting the impact of elevated intraocular pressure on vessel diameter and blood flow, which manifests as decreased CI on CEUS [ 25 ].
Retinal reattachment within 4 weeks or less is associated with a more favorable prognosis in canine and feline patients [ 10 , 26 ]. CEUS represents a reliable method for assessing retinal vitality and may help predict the likelihood of success or failure of vitreoretinal surgery, even when the duration of detachment is unkown [ 10 ].
In cases of neoplasia in canine and feline eyes, CEUS has been suggested to be superior to Color and Power Doppler ultrasonography for detecting blood flow within intraocular masses and identifying increased vascularization in suspected neoplasia [ 20 , 21 ].
Similar to prior reports [ 19 , 27 ], the cases of melanoma in this series demonstrated centripetal enhancement, a homogeneous pattern, strong CI, and shorter contrast retention in the lesion than in the surrounding tissue. Differing from the prior study [ 27 ], contrast uptake was observed in these lesions slightly earlier than the surrounding tissue. Wash‐in and WO characteristics were inconsistent across studies; however, similar to the cases in the present study, there was an overall tendency toward rapid WI and rapid WO [ 18 , 19 ]. Another publication [ 16 ] highlighted the potential of CEUS in the assessment of choroidal melanoma, emphasizing its ability to demonstrate the pronounced vascularization typical of melanoma and to distinguish it from choroidal nevi, as well as its utility in monitoring treatment response after radiotherapy through the detection of a gradual decline in tumor blood flow. In the present case series, two melanomas were evaluated, which exhibited consistent enhancement patterns despite differing locations. Although no cases of feline diffuse iris melanoma were included, the application of CEUS in this diagnostically challenging condition warrants further investigation.
In human ophthalmology, CEUS is recognized as a suitable imaging technique for the diagnosis of orbital space‐occupying pathologies [ 19 ]. For differentiating benign from malignant intraocular tumors, a sensitivity of 98.3% and specificity of 100% has been reported [ 18 ]. Malignant tumors (e.g., choroidal melanoma, choroidal metastasis and retinoblastomas) are typically characterized by a rich blood supply, with CEUS demonstrating rapid WI, short time‐to‐peak, strong hyperechoic signal, and rapid WO [ 19 ]. This behavior reflects tumor‐induced angiogenesis, resulting in abundant abnormal arterial and venous vessels with high blood volume. In contrast, benign lesions are characterized by low‐velocity flow within thin‐walled venous vasculature, which explains their distinct enhancement patterns on CEUS. Benign lesions such as hemangiomas, melanocytomas, calcifications and pseudotumors, typically exhibit rapid WI with slow WO [ 18 , 19 ].
In our case series, the canine pseudotumor exhibited a rapid homogeneous, centripetal enhancement, with the central region displaying lower contrast intensity compared to the periphery and a rapid WO. A direct comparison of WI and WO characteristics with surrounding tissue was not feasible as we focused on imaging of the lesion's perfusion as accurately as possible; the imaging window included only the pseudotumor without adjacent reference tissue. The centrally reduced contrast intensity may reflect areas of central necrosis within the lesion. This interpretation is supported by previous findings, where “filling defects” have been proposed as a possible imaging correlate of central necrosis. Notably, even in cases with histopathologically confirmed central necrosis, such imaging features may not always be explicitly emphasized, highlighting the subtlety of this finding on CEUS [ 19 ].
Overall, similar CEUS characteristics in inflammatory pseudotumors have been reported, including rapid WI followed by homogeneous enhancement and, different to our case, a slow WO with lesion enhancement exceeding that of surrounding tissue. Histopathological results in their study revealed sporadic necrosis and chronic inflammatory cell infiltration [ 19 ].
In comparison, the present case of pseudotumor and a patient diagnosed with adenocarcinoma were located at the same anatomical site (nictitating membrane) and presented with a similar mass effect on conventional ultrasound. Despite these similarities in location and ultrasonographic appearance, the underlying pathologies differed, with one being neoplastic and the other inflammatory. Notably, CEUS contrast behavior differed between the two lesions, and both diagnoses were confirmed histopathologically. The lymphohistiocytic pseudotumor demonstrated a predominantly homogeneous, centripetal enhancement pattern with progressively decreasing contrast intensity toward the center, without marked intralesional heterogeneity or clear early focal vascular irregularities. Furthermore, the lesion exhibited a rapid WI followed by a rapid WO.
In contrast, the nictitating membrane adenocarcinoma showed a more heterogeneous enhancement behavior, with initial enhancement of the surrounding tissue followed by early visualization of superficial tumor vessels. Enhancement within the lesion was irregular and centripetal, followed by a brief peak phase and earlier central wash‐out. Peripheral vessels remained visible for a longer duration, with intermittent centripetal filling. The adenocarcinoma also demonstrated a rapid WI, but in contrast to the pseudotumor, it showed a delayed WO. Overall, the CEUS findings in the present cases only partially corresponded to the differentiating features described in human medicine. While rapid WI was observed in both the pseudotumor and the adenocarcinoma, WO characteristics differed from the commonly described human pattern, with rapid WO in the pseudotumor and delayed WO in the adenocarcinoma. Thus, WI and WO characteristics alone did not differentiate inflammatory from neoplastic disease in these two cases according to the criteria described in human medicine [ 18 , 19 ]. Instead, the observed differences in enhancement pattern and vascular architecture may provide additional information for differentiation.
Several factors may limit direct comparison with the human studies described above. Definitions and time thresholds used to categorize WI and WO as rapid, slow, or delayed may differ between studies, and differences in tumor biology and vascular architecture between human and veterinary patients may influence contrast enhancement behavior. Furthermore, the available studies describe CEUS characteristics of inflammatory pseudotumors, whereas specific CEUS characteristics of adenocarcinomas have not been reported [ 18 , 19 ]. In addition, one study [ 18 ] assessed contrast kinetics using quantitative time‐intensity curve analysis, whereas the present study relied on qualitative assessment, which may have influenced the classification of WI and WO. Given these limitations and the small number of cases, these observations should be interpreted cautiously and require confirmation in larger prospective studies.
In human medicine, optic nerve lymphomas and meningiomas are considered particularly suitable for CEUS diagnostics due to their pronounced vascularization [ 16 ]. In the present study, both neoplasms were visualized with CEUS, which provided additional information on their enhancement characteristics. The centrifugal enhancement pattern in the lymphoma case was similar to that reported in canine and feline mediastinal lymphomas [ 28 ]. It is hypothesized that this reflects the lymph node‐like angioarchitecture of these tumors, with perfusion maintained by a centrally entering hilar vessel [ 28 , 29 ]. While meningiomas have been proposed as suitable CEUS lesions due to their pronounced vascularization, their specific CEUS characteristics remain undescribed, highlighting the need for further investigation of this clinically relevant neoplasia.
Strong CEUS enhancement in inflammatory lesions is primarily attributed to inflammatory hyperemia and vasodilation, leading to increased regional perfusion. However, enhancement is not uniformly present across all inflammatory conditions [ 23 ]. To date, no studies have described the use of CEUS in inflammatory orbital or intraocular lesions. In the present study, variable degrees of contrast intensity were observed in inflammatory lesions, although a tendency toward stronger enhancement with a rapid WI and a delayed WO was noted by the authors. This is in line with the expected hyperemic response in actively inflamed tissue. The variability in enhancement may be explained by differences in the underlying pathophysiological stage and severity of inflammation, as well as the affected tissue type. Acute inflammatory processes with pronounced vasodilation are likely to exhibit stronger and more homogeneous enhancement, whereas more chronic or less active inflammatory conditions may show reduced or heterogeneous enhancement patterns due to vascular remodeling or tissue damage [ 23 ].
The observed enhancement of abscess capsules with sparing of the abscess content aligns with previous findings using contrast‐enhanced MRI [ 30 , 31 ]. Dennis [ 11 ] reported an ocular abscess initially misdiagnosed as a neoplasm on conventional ultrasound, which was correctly identified by capsule enhancement on MRI. Two cases in this series demonstrated some degree of contrast uptake within the abscess, although the capsule typically showed stronger peripheral enhancement. Intralesional contrast enhancement may be attributed to vascularized septa within the abscess [ 32 ]. It is important to note that two abscesses in the included cases were undetectable by both B‐mode ultrasonography and CEUS, indicating that the advantages of CEUS over conventional B‐mode imaging should be interpreted cautiously for orbital abscesses.
Regarding myositis and steatitis, Fischer et al. [ 31 ] reported abnormal enhancement patterns and swelling using contrast‐enhanced MRI. In human medicine, CEUS has been shown to be more effective than conventional ultrasonography for diagnosing myositis due to its ability to quantify inflammation‐induced muscle hyperperfusion in acute cases [ 33 , 34 ]. In this study, however, no consistent contrast enhancement characteristic was observed, suggesting that the additional diagnostic benefit of CEUS over B‐mode ultrasonography remains questionable for these lesions.
The limitations of this case series include its retrospective design and the fact that the operators were not blinded to the suspected diagnosis, which may have introduced potential bias. Additionally, varying contrast‐medium dosages and ultrasound probes were used. However, both dosages and probes used in this study provided satisfactory contrast enhancement. Most animals underwent CEUS without sedation, but in the sedated or anesthetized cases, cardiovascular alterations may have influenced perfusion.
The limited sample size precluded species‐specific analyses, which could be valuable in future studies evaluating conditions such as feline diffuse iris melanoma or FROMS. In some cases, histopathological confirmation was unavailable and the diagnosis was based solely on therapeutic response. Furthermore, many animals had multiple concurrent ophthalmic pathologies, which may have affected the CEUS findings.
Finally, quantitative analysis of time‐intensity curves was not performed, although Blohm et al. [ 15 ] have shown that qualitative and quantitative results can differ. Given that the primary goal of this investigation was to describe the practical applicability of CEUS, the study focused on qualitative assessment, acknowledging its inherent subjectivity. However, the reported time intervals (in seconds) in this study should be interpreted cautiously, as no formal quantitative time‐intensity curve analysis with region‐of‐interest‐based measurements was performed. The provided values are based on observational assessment of the recorded CEUS examinations and should be considered approximate reference points rather than precise quantitative measurements. Accordingly, they are intended primarily to complement the qualitative interpretation of contrast‐enhancement dynamics and to facilitate reader understanding and comparison between cases.
This study provides initial insights into the perfusion characteristics of various orbital and intraocular pathologies using CEUS. Further research is warranted to evaluate the potential of CEUS to differentiate or diagnose specific pathologies based on their enhancement characteristics.
Considering the higher costs of contrast agents and the need for specialized software, the additional diagnostic benefit of CEUS over B‐mode ultrasonography for assessing inflammatory lesions such as abscesses, uveitis, endophthalmitis, myositis and steatitis remains uncertain. In contrast, CEUS consistently detected persistent retinal perfusion in retinal detachments and demonstrated distinct enhancement characteristics in neoplastic lesions, likely reflecting tumor vascular characteristics, which may facilitate differentiation of neoplasia types in future clinical applications.
5. Conclusion
This case series highlights the utility of CEUS for visualizing a range of orbital and intraocular pathologies. In neoplastic lesions, CEUS provides distinct enhancement characteristics, aids in precise localization, and demonstrates tissue perfusion characteristics. These features may facilitate more accurate differentiation of pathologies, supporting the role of CEUS as a valuable adjunct to conventional ophthalmic ultrasonography.
Author Contributions
Janneke I. Ortner: conceptualization, writing – original draft, data curation, formal analysis. Katharina M. Hittmair: conceptualization, data curation, supervision, writing – review and editing. Barbara Nell: conceptualization, supervision, writing – review and editing. Klaas‐Ole Blohm: conceptualization, writing – review and editing, data curation, supervision.
Disclosure
The authors have not used AI to generate any part of the manuscript.
Ethics Statement
The owners provided written consent for the publication of patient data for research purposes.
Conflicts of Interest
The authors declare no conflicts of interest.
Acknowledgments
The authors have nothing to report. Open Access funding provided by Veterinarmedizinische Universitat Wien.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.