3D-CTA在颅内动脉瘤破裂开颅手术中的应用价值

目的探讨三维血管CT造影（3D-CTA）在颅内动脉瘤破裂开颅手术中的应用价值。方法经手术证实的颅内动脉瘤破裂导致蛛网膜下腔出血（SAH）或颅内血肿患者65例,术前均行3D-CTA检查并进行动脉瘤手术模拟,部分患者术前行DSA检查。将患者术前3D-CTA、术前DSA、术中所见进行比较,分析3D-CTA的临床应用价值。结果 65例患者共有动脉瘤68枚,3D-CTA发现65枚,诊断阳性率为95.59%,特异性为100%。3D-CTA可清晰显示动脉瘤位置、大小、形态、瘤顶指向、瘤颈宽窄、载瘤动脉、动脉瘤与周围血管及骨结构关系,且与术中所见基本一致。结论 3D-CTA是一种准确、快捷、微创的诊断颅内动脉瘤方法,能够提供足够信息指导动脉瘤的外科手术治疗。     

三维CT血管造影术在急性蛛网膜下腔出血颅内动脉瘤诊断中的应用

目的探讨三维CT血管造影术（3D-CTA）在急性蛛网膜下腔出血（SAH）颅内动脉瘤诊断中的应用。方法采用3D-CTA和DSA对26例非外伤性SAH患者进行检查，3D-CTA通过最大密度投影（MIP）、表面遮盖法重建（SSD）和容积重建术（VRT）方法获得图像．根据3D-CTA和DSA所获得的关于动脉瘤的位置、大小等进行术前评估。结果在26例中24例3D-CTA检测出27个动脉瘤，瘤体直径3-2mm，1例后交通动脉瘤3D-CTA不能证实，1例未检出动脉瘤；14例行DSA检查，其中1例未检出动脉瘤而通过3D-CTA发现，1例右椎动脉梭形动脉瘤因DSA行右椎动脉造影失败而通过3D-CTA发现。12例仅凭3D-CTA手术，3D-CTA在检查动脉瘤的位置、大小、瘤体方向及对载瘤动脉和分支动脉的形态描述均优于DSA，它在诊断颅内动脉瘤的敏感性和特异性分别为96％和100％。结论3D-CTA是一种准确、价廉、非侵袭性的诊断颅内动脉瘤SAH的方法，在动脉瘤的急诊手术时较DSA更具优越性。     

三维CT血管造影术在颅内动脉瘤破裂早期诊治中的价值(附348例报告)

目的评价三维CT血管造影术（3D-CTA）在颅内动脉瘤破裂早期诊断和治疗中的临床应用价值。方法对419例自发性蛛网膜下腔出血病例全部行3D-CTA检查，其中阴性病例再行DSA检查，对确诊为颅内动脉瘤的病例行显微外科手术或介入治疗。结果345例经3D-CTA检查阳性中检出动脉瘤365个，75例阴性病例中DSA证实仅有3例漏诊。348例动脉瘤患者共检测出动脉瘤368个，术中见动脉瘤位置及瘤体、瘤颈和周围解剖结构的关系与术前3D-CTA显示一致。术后病人3D-CTA随访，与术前比较，动脉瘤均夹闭完全、确实。结论3D-CTA是一种方便、可靠、快捷的诊断方法，可以作为颅内动脉瘤破裂诊治的首选影像检查。并且在术中及术后复查随访研究方面也具有重要的临床应用价值。     

3D-CTA在破裂颅内动脉瘤诊断和手术中的应用

目的探讨三维CT血管造影(3D-CTA)对破裂颅内动脉瘤诊治的价值。方法 21例破裂颅内动脉瘤均行3D-CTA检查,8例同时行常规DSA检查,20例行显微手术动脉瘤夹闭。结果 21例共计发现25个动脉瘤,3D-CTA检查发现24个动脉瘤,在1例多发动脉瘤中3D-CTA遗漏1个大脑中动脉瘤,DSA能显示该动脉瘤,同时发现载瘤动脉存在脑血管痉挛。20例24个动脉瘤直接手术夹闭,术后存活14例(恢复良好12例,差2例),死亡6例,术中探查发现动脉瘤数目、位置、载瘤血管、瘤顶指向、瘤体及瘤顶大小与3D-CTA显示基本吻合,无假阳性。结论 3D-CTA诊断颅内动脉瘤具有微创、快捷、安全、可靠的优点,并可显示动脉瘤立体结构,可作为重症破裂动脉瘤及年老体弱患者的首选影像学诊断方法,术者可依据3D-CTA提供的信息指导手术。     

3D-CTA在急性破裂颅内动脉瘤诊断和治疗中的应用

目的探讨三维CT血管造影(3D-CTA)在颅内动脉瘤破裂急性期的临床诊断价值。方法148例疑为颅内动脉瘤破裂的自发性蛛网膜下腔出血患者,进行3D-CTA检查,时间分别在发病后2h到4d;其中6例在3D-CTA之前行数字减影脑血管造影(2D-DSA)检查,142例在3D-CTA之后行DSA检查,扫描图像后经计算机工作站处理。原始图像三维后处理技术采用容积重建(VR)和最大密度投影(MIP),以VR为主。后处理图像与DSA图像分别由两位放射科医生和神经外科医生用双盲法进行分析。对动脉瘤治疗采用夹闭和血管内栓塞两种技术。结果经3D-CTA、DSA和手术或栓塞证实共发现112例130个动脉瘤,大小自1.1～28mm,其中单发动脉瘤97例,多发15例33个动脉瘤。在112例动脉瘤中,3D-CTA发现112例128个动脉瘤,漏诊多发动脉瘤中的2个,敏感度为98.5%,特异度94.7%,准确度97.6%,阳性预测值98.5%,阴性预测值94.7%;而DSA发现动脉瘤109例127个动脉瘤,漏诊3例3个动脉瘤,敏感度为97.7%,特异度100%,准确度98.2%,阳性预测值100%,阴性预测值为92.3%。在3D-CTA上均可清晰或较清晰显示出瘤颈与载瘤动脉的关系,占98.4%;而DSA能清晰显示瘤颈与载瘤动脉关系仅占40.9%,两者有统计学意义(x2= 5.545,P<0.05)。结论3D-CTA对颅内动脉瘤具有极高的敏感性和特异性,并具有快捷、经济和相对无创等优点,对颅内动脉瘤破裂急性期的诊断优于2D-DSA。     

三维CT血管造影在颅内动脉瘤诊治中的临床价值

目的探讨三维CT血管造影(3D-CTA)在颅内动脉瘤诊治中的临床应用价值。方法回顾性分析自2006年1月至2009年3月以来72例颅内动脉瘤患者的3D-CTA及DSA影像学资料,3D-CTA及DSA图像分别由两位神经外科医师及放射科医师采用双盲法进行对比分析。结果经手术证实72例患者共85个动脉瘤,其中单发动脉瘤61例;多发动脉瘤11例,9例发现2个动脉瘤,2例发现3个动脉瘤。3D-CTA发现67例80个动脉瘤,而DSA发现70例83个动脉瘤。动脉瘤体最大径及瘤颈宽度的测量值在CTA与DSA组间比较无显著性差异(P0.05)。3D-CTA的敏感性及特异性分别为97.65%及94.12%,而DSA的敏感性及特异性则分别为98.82%及97.65%,两组间也无显著差异(P均0.05)。结论 3D-CTA是一种快速、价廉的无创性检查技术,对颅内动脉瘤诊断的敏感性及特异性较高,并可准确显示动脉瘤的位置、形态及大小,较好评估动脉瘤体、载瘤动脉及周围血管之间的关系,从而为选择适当的手术治疗方案提供了可靠的直观依据。     

颅内动脉瘤三维CT血管成像的临床研究

目的 评价和对比3D-CTA、MRA和DSA对颅内动脉瘤诊断的临床价值。方法 对96例可疑动脉瘤患者行3D-CTA,MRA和DSA检查。结果 共发现129个动脉瘤。3D-CTA发现的最小动脉瘤大小为1.6mm×1.7mm×2.0mm。3D-CTA对动脉瘤诊断的灵敏性和特异性均为100％,而MRA则分别为95.3％和97.6％,DSA为100％和97.7％;对载瘤动脉和分枝动脉的形态描述明显优于MRA和DSA(分别为P<0.05和P<0.01);在阐明动脉瘤颈的形态上明显优于MRA和DSA(P<0.01);对动脉瘤血栓化和钙化的检出率明显高于MRA和DSA(P<0.001)。3D—CTA在108例(83.7％)动脉瘤临床治疗方案的选择上提供了重要依据。结论 3D—CTA在动脉瘤检出及其特征描述上优于MRA和DSA。3D—CTA对颅内动脉瘤的临床治疗有重要的指导作用。     

DSA与MRI或MRA双三维影像融合技术要点及在颅内动脉瘤诊治中的应用

目的探讨DSA与MRI或MRA双三维影像融合技术条件与要点及对颅内大与巨大型动脉瘤诊断、对脑深部微小动脉瘤与静脉瘤实施神经导航手术的价值。方法早期应用手工操作,目前在Siemens Artis Zee Biplane双大平板DSA机的SystemSyngo X-WP三维后处理工作站上,将符合三维融合条件的DSA与MRI或MRA影像数据,利用Inspace 3D-3D-Fustion软件分析合并数据后,将DSA与MRI或MRA双三维影像进行融合,获得融合后影像供临床诊断、评估颅内大与巨大型动脉瘤以及治疗脑深部小型动脉瘤、静脉瘤时输入神经导航实施手术。结果对1例左颈内动脉后交通巨大型动脉瘤伴血栓形成病人,通过DSA与MRI或MRA双三维融合影像,提高了巨大型动脉瘤血管內治疗前后对瘤体大小及瘤内血栓与临床占位效应相关性的认识;对1例脑室岀血铸型病人,经DSA确诊为moyamoya病合并胼胝体下室旁脉络膜后动脉血流相关性动脉瘤及1例脑深部动静脉畸形合并血流相关性静脉瘤病人成功实施了神经导航手术。结论 DSA与MRI或MRA双三维影像融合是一项用特制软件后处理新技术,融合后三维影像对颅内大与巨大型动脉瘤的诊断有新认识,发现DSA影像瘤体小于MRI影像瘤体而大于MRA影像瘤体,以及对脑深部血流相关性动脉瘤及静脉瘤融合数据输入神经导航实施手术有很高应用价值。     

16层螺旋CT 3D-CTA在颅内动脉瘤中的诊断及临床应用价值

目的探讨三维CT血管造影（three dimensional computed tomographic angiography，3D-CTA）在颅内动脉瘤的临床应用及其价值。方法对自发性蛛网膜下腔出血及怀疑颅内动脉瘤的患者53例，使用SIEMENS SOMATOM Sensation 16层螺旋CT扫描仪行3D-CTA检查（时间在发病后4h～3d），并行数字减影血管造影（digital subtraction angiography，DSA）检查；3D-CTA图像与DSA图像由神经外科医师和放射科医师用双盲法共同进行分析。结果经3DICTA、DSA和手术共同证实发现44例共49个动脉瘤，动脉瘤大小为1．7～25mm，其中单发动脉瘤36例，多发5例（1例为3个动脉瘤，4例为2个动脉瘤）；在44例动脉瘤患者中3D-CTA发现42例47个动脉瘤；DSA发现43例48个动脉瘤；动脉瘤的瘤体最大径及瘤颈最大径3D-CTA测量值与DSA测量值比较无显著性差异（t=0．59和t=0．49，P均〉0．05）；53例病情轻重不一患者在行3D-CTA检查过程中病情无加重或无其他意外发生。结论3D-CTA对颅内动脉瘤具有快捷、经济、安全和微创等优点，并有通过一次注射对比剂扫描即可从任意角度观察所显示的颅内动脉瘤的细节及与骨性结构的关系等优点，但存在无法依时间顺序分别显示动脉、毛细血管和静脉，无法分清血流方向及显示一些重要的小血管和重要的穿通支如脉络膜前动脉、丘脑穿通动脉等，也无法在血管内操作等不足之处；在诊断和治疗颅内动脉瘤的应用中与DSA检查互补也可得到颅内动脉瘤更完整的信息。     

CT,MRA和DSA对颅内动脉瘤的诊断分析

目的 探讨CT、MRA和DSA对颅内动脉瘤的诊断价值。方法 回顾性分析247例颅内动脉瘤病人的临床资料、影像特点。结果 247例患者均经手术证实为动脉瘤。所有患者均行CT扫描检查,发现单发灶性积血161例,多灶性积血9例,并发颅内血肿14例,6例因头部外伤行头颅CT扫描发现动脉瘤。阳性率为71.25％。DSA检查177例,发现动脉瘤166例,阳性率为93.79％。MRI检查140例,其中MRA检查110例,发现动脉瘤131例,阳性率为93.57％。结论 动脉瘤有特征性CT、MRA和DSA表现。CT可动态、无创观察病情变化,有助于早期发现动脉瘤,反映其真实大小,并可了解动脉瘤破裂后的出血量和范围以及脑积水和脑水肿的程度。MRA能显示动脉瘤的全部和周围组织的关系,尤其适用于比较大的动脉瘤。MRA安全且可三维旋转以观察瘤蒂和动脉瘤内的血流情况。CT、MRA和DSA联合应用,有利于对动脉瘤的全面诊断,且彼此不能完全取代。     

前循环巨大动脉瘤的显微手术治疗

目的：改进颅内巨大动脉瘤的显微手术技术,以提高颅内巨大动脉瘤的治疗效果。方法：回顾性分析10例前循环巨大颅内动脉瘤的临床资料和手术效果,其中3例为双侧多发动脉瘤。术中应用载瘤动脉近端临时阻断、颈部颈内动脉暂时夹闭、动脉瘤颈逐步缩窄、动脉瘤体穿刺抽吸减压、动脉瘤体切除等技术,动脉瘤夹闭后以可吸收再生氧化纤维素包裹动脉瘤,并用丝线将动脉瘤夹固定于颅底硬膜上并,术程中始终应用生理盐水加维生素C及罂粟碱冲洗。结果：10例动脉瘤手术全部成功夹闭,其中3例多发动脉瘤均一期手术成功夹闭。出院时优良者8例,轻残者2例。结论：颅内巨大动脉瘤通过术前详细的手术计划,术中改进的手术技术和预防术后血管痉挛药物的应用可以明显提高颅内动脉瘤的手术治疗效果,减少术后并发症。应用丝线固定动脉瘤夹在最大程度上避免了术后因动脉瘤夹的滑脱而导致患者颅内大出血死亡。     

Non-contrast 3D time-of-flight magnetic resonance angiography for visualization of intracranial aneurysms in patients with absolute contraindications to CT or MRI contrast

The preoperative evaluation of patients with intracranial aneurysms typically includes a contrast-enhanced vascular study, such as computed tomography angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography. However, there are numerous absolute and relative contraindications to the administration of imaging contrast agents, including pregnancy, severe contrast allergy, and renal insufficiency. Evaluation of patients with contrast contraindications thus presents a unique challenge. We identified three patients with absolute contrast contraindications who presented with intracranial aneurysms. One patient was pregnant, while the other two had previous severe anaphylactic reactions to iodinated contrast. Because of these contraindications to intravenous contrast, we performed non-contrast time-of-flight MRA with 3D reconstruction (TOF MRA with 3DR) with maximum intensity projections and volume renderings as part of the preoperative evaluation prior to successful open surgical clipping of the aneurysms. In the case of one paraclinoid aneurysm, a high-resolution non-contrast CT scan was also performed to assess the relationship of the aneurysm to the anterior clinoid process. TOF MRA with 3DR successfully identified the intracranial aneurysms and adequately depicted the surrounding microanatomy. Intraoperative findings were as predicted by the preoperative imaging studies. The aneurysms were successfully clip-obliterated, and the patients had uneventful post-operative courses. These cases demonstrate that non-contrast imaging is a viable modality to assess intracranial aneurysms as part of the surgical planning process in patients with contrast contraindications. TOF MRA with 3DR, in conjunction with high-resolution non-contrast CT when indicated, provides adequate visualization of the microanatomy of the aneurysm and surrounding structures.     

Magnetic resonance angiography image guidance for the microsurgical clipping of intracranial aneurysms: a report of two cases

To describe the integration of magnetic resonance angiography (MRA) in neuronavigation procedures for microsurgery of intracranial aneurysms. MRA was combined with standard magnetic resonance image (MRI) acquisition in the image-guided planning for the microsurgical clipping of a saccular aneurysm in two patients (one 3-mm large middle cerebral artery and one 8-mm large pericallosal artery aneurysm, diagnosed by catheter angiography in both patients) using two different neurosurgical navigation systems. Conventional 3-D T1-weighted MRI with gadolinium and MRA pulse sequences were acquired in frameless stereotactic conditions the day before surgery and thereafter registered, allowing the definition a minimally invasive straight trajectory to the aneurysm neck. MRA-guided neurosurgery allowed a direct approach to the aneurysms at their proper location, reducing the invasiveness of the approach by tailoring the bone opening and reducing the duration and extension of brain retraction. The technique also avoided unnecessary dissection and exposure of the main trunks and collateral vessels. The aneurysms were successfully eradicated without complication. Integration of MRA in the planning and neuronavigation procedure for intracranial aneurysms may minimize the morbidity related to the surgical approach. This technique may be applicable more routinely using standard neuronavigation equipment.     

Magnetic resonance angiography image guidance for the microsurgical clipping of intracranial aneurysms: a report of two cases

Abstract

To describe the integration of magnetic resonance angiography (MRA) in neuronavigation procedures for microsurgery of intracranial aneurysms. MRA was combined with standard magnetic resonance image (MRI) acquisition in the image-guided planning for the microsurgical clipping of a saccular aneurysm in two patients (one 3-mm large middle cerebral artery and one 8-mm large pericallosal artery aneurysm, diagnosed by catheter angiography in both patients) using two different neurosurgical navigation systems. Conventional 3-D T1-weighted MRI with gadolinium and MRA pulse sequences were acquired in frameless stereotactic conditions the day before surgery and thereafter registered, allowing the definition a minimally invasive straight trajectory to the aneurysm neck. MRA-guided neurosurgery allowed a direct approach to the aneurysms at their proper location, reducing the invasiveness of the approach by tailoring the bone opening and reducing the duration and extension of brain retraction. The technique also avoided unnecessary dissection and exposure of the main trunks and collateral vessels. The aneurysms were successfully eradicated without complication. Integration of MRA in the planning and neuronavigation procedure for intracranial aneurysms may minimize the morbidity related to the surgical approach. This technique may be applicable more routinely using standard neuronavigation equipment.     

Imaging of subarachnoid hemorrhage

Even if acute subarachnoid hemorrhage (SAH) accounts for only 5% of strokes, its diagnosis is very important because its clinical consequences can be tragic. Recent technological advances in medical imaging have improved diagnostic and therapeutic management of patients with SAH. Nonenhanced CT of the head is the initial imaging modality in suspected SAH for the detection of ruptured intracranial aneurysms. Digital subtraction angiography (DSA) remains the reference exam. Multidetector row CT angiography may potentially replace DSA in the emergency setting, as it provides image data that allows evaluating aneurysmal morphology, the neck size or the visualization of vessels in the vicinity of the aneurysm. For SAH unrelated to aneurysm rupture (15% of cases), MRI and MRA can be added to the diagnostic work-up in order to exclude other differential diagnoses such as venous thrombosis or angiitis. Finally, transcranial color-coded duplex sonography, CT, or MRI are used in clinical practice in order to detect aggravating factors of SAH like hydrocephalus or vasospasm.     

颅内动脉瘤3D-CTA诊断效能的临床研究

目的 评价三维CT血管成像(3D—CTA)在外科治疗颅内动脉瘤中的诊断效能。方法 24例可疑动脉瘤患者行脑血管造影、3D—CTA、MRA和DSA检查。结果 本组共发现28个动脉瘤。21例病人有一个，2例有两个，1例有三个动脉瘤。3D—CTA发现瘤体呈球形为20个、椭圆形5个、分叶形3个。手术暴露的24个动脉瘤，其瘤体形态与3D—CTA发现完全吻合。动脉瘤颈平均直径为5.9mm，最小为1.6mm，最大为13．7mm。根据3D—CTA计算的动脉瘤颈结果与手术发现非常接近。3D—CTA对载瘤动脉和分枝动脉的形态描述明显优于脑血管造影、MRA和DSA。结论 3D—CTA在了解动脉瘤的三维结构和制定手术治疗方案有重要辅助作用。     

129例颅内大型和巨大型动脉瘤的显微手术治疗

目的探讨颅内大型和巨大型动脉瘤的临床特点以及术中处理技巧,提高手术疗效。方法总结分析我院129例颅内大型及巨大型动脉瘤的手术经验。其中瘤颈部夹闭110例,夹闭+包裹9例,瘤体电凝后包裹3例,载瘤动脉夹闭2例,动脉瘤切除2例,巨大动脉瘤切除后同时行吻合2例,动脉瘤旷置+颅外-颅内高流量架桥术1例。手术采用近侧载瘤动脉暂时性阻断、动脉瘤内减压、动脉瘤重塑等技术,其中10例患者术中应用神经内镜辅助夹闭动脉瘤和Transonic HT313血流量仪检测载瘤动脉血流情况。结果术后根据改良Rankin评分,恢复良好116例(89.9%),功能障碍9例(7.0%),死亡4例(3.1%)。结论通过术前完善的影像学判断及详细的手术计划,熟悉动脉瘤区域的解剖关系,进行有效的脑保护,使用多手段处理动脉瘤的技术,可明显提高颅内大型和巨大型动脉瘤手术治疗效果;术中应用神经内镜辅助夹闭动脉瘤和血流量仪检测载瘤动脉血流技术有助于减少术后并发症的发生。     

Giant unruptured anterior communicating artery aneurysm presenting with seizure.

Giant aneurysms of the anterior communicating artery (AComA) are rare. The clinical presentation of giant AComA aneurysms is usually associated with the mass effect of the space-occupying lesion or with subarachnoid haemorrhage. A giant AComA aneurysm presenting with a seizure has only been reported twice previously. We report a 70-year-old female patient, in whom a single seizure was the only symptom of a giant AcomA aneurysm, with no neurological deficit. The diagnosis of unruptured giant AComA aneurysm was made with cranial CT, MRI and angiography. The patient refused surgical intervention, was treated with anti-epileptic therapy and has been asymptomatic for 7 months. We suggest that elderly patients presenting with a first seizure need detailed evaluation and giant aneurysms, which may be confused with other intracranial space-occupying lesions, need to be considered in the differential diagnosis.     

Successful serial imaging of the mouse cerebral arteries using conventional 3-T magnetic resonance imaging

Serial imaging studies can be useful in characterizing the pathologic and physiologic remodeling of cerebral arteries in various mouse models. We tested the feasibility of using a readily available, conventional 3-T magnetic resonance imaging (MRI) to serially image cerebrovascular remodeling in mice. We utilized a mouse model of intracranial aneurysm as a mouse model of the dynamic, pathologic remodeling of cerebral arteries. Aneurysms were induced by hypertension and a single elastase injection into the cerebrospinal fluid. For the mouse cerebrovascular imaging, we used a conventional 3-T MRI system and a 40-mm saddle coil. We used non-enhanced magnetic resonance angiography (MRA) to detect intracranial aneurysm formation and T2-weighted imaging to detect aneurysmal subarachnoid hemorrhage. A serial MRI was conducted every 2 to 3 days. MRI detection of aneurysm formation and subarachnoid hemorrhage was compared against the postmortem inspection of the brain that was perfused with dye. The imaging times for the MRA and T2-weighted imaging were 3.7±0.5 minutes and 4.8±0.0 minutes, respectively. All aneurysms and subarachnoid hemorrhages were correctly identified by two masked observers on MRI. This MRI-based serial imaging technique was useful in detecting intracranial aneurysm formation and subarachnoid hemorrhage in mice.     

Totally thrombosed giant P2 aneurysm: a case report and review of literature.

The diagnosis and treatment of intracranial saccular giant aneurysms is still difficult despite developments in neuroradiology, neuroanesthesiology and micro-neurosurgery. These aneurysms are usually located on major intracranial arteries and are rarely on distal branches of these arteries. An extra-axial 4 x 5 cm mass lesion in the left mediobasal temporal region was detected on the CT and MRI examinations of a 37 year old male patient who was admitted to our institution with headache and slight right-sided hemiparesis lasting for 2 months. The lesion was avascular on angiography. Surgery proved that the lesion was a totally thrombosed giant aneurysm of the P2 segment of posterior cerebral artery (PCA). The P2 segment was clipped proximal to the aneurysm with pterional-transsylvian approach and the aneurysm was totally excised. Giant aneurysms of the P2 segment are rare and 15 cases have been reported in the literature. This report presents a rarely seen totally thrombosed giant P2 aneurysms and discusses the difficulties in diagnosis and treatment.