A multimodal nano agent for image-guided cancer surgery

Intraoperative imaging technologies including computed tomography and fluorescence optical imaging are becoming routine tools in the cancer surgery operating room. They constitute an enabling platform for high performance surgical resections that assure local control while minimizing morbidity. New contrast agents that can increase the sensitivity and visualization power of existing intraoperative imaging techniques will further enhance their clinical benefit. We report here the development, detection and visualization of a dual-modality computed tomography and near-infrared fluorescence nano liposomal agent (CF800) in multiple preclinical animal models of cancer. We describe the successful application of this agent for combined preoperative computed tomography based three-dimensional surgical planning and intraoperative target mapping (>200 Hounsfield Units enhancement), as well as near-infrared fluorescence guided resection (>5-fold tumor-to-background ratio). These results strongly support the clinical advancement of this agent for image-guided surgery with potential to improve lesion localization, margin delineation and metastatic lymph node detection.     

三维可视化技术在复杂骨与软组织肿瘤手术中的临床应用

目的:探讨三维可视化技术在复杂骨与软组织肿瘤外科手术治疗中的临床应用价值。方法:回顾性研究。纳入2019年4—12月中国科学技术大学附属第一医院(西区)骨科11例复杂骨与软组织肿瘤患者的临床资料,其中男5例、女6例,年龄16～67(52.6±15.9)岁。11例患者术前均行CT常规二维扫描及三维可视化技术重建,于重建模...     

2D/3D registration of endoscopic ultrasound to CT volume data

This paper describes a computer-aided navigation system using image fusion to support endoscopic interventions such as the accurate collection of biopsy specimens. An endoscope provides the physician with real-time ultrasound (US) and a video image. An image slice that corresponds to the corresponding image from the US scan head is derived from a preoperative computed tomography (CT) or magnetic resonance image volume data set using oblique reformatting and displayed side by side with the US image. The position of the image acquired by the US scan head is determined by a miniaturized electromagnetic tracking system (EMTS) after calibrating the endoscope's scan head. The transformation between the patient coordinate system and the preoperative data set is calculated using a 2D/3D registration. This is achieved by calibrating an intraoperative interventional CT slice with an optical tracking system (OTS) using the same algorithm as for the US calibration. The slice is then used for 2D/3D registration with the coordinate system of the preoperative volume. The fiducial registration error (FRE) for the US calibration was 2.0 mm +/- 0.4 mm; the interventional CT FRE was 0.36 +/- 0.12 mm; and the 2D/3D registration target registration error (TRE) was 1.8 +/- 0.3 mm. The point-to-point registration between the OTS and the EMTS had an FRE of 0.9 +/- 0.4 mm. Finally, we found an overall TRE for the complete system to be 3.9 +/- 0.6 mm.     

Tracer-cocktail injections for combined pre- and intraoperative multimodal imaging of lymph nodes in a spontaneous mouse prostate tumor model

To improve surgical guidance toward prostate draining lymph nodes, we investigate the potential of intraoperative fluorescence imaging and combined pre- and intraoperative multimodality imaging approaches. Transgenic adenocarcinoma mouse prostate mice with spontaneous prostate tumors are injected intratumorally with: 1. a cocktail of patent blue (Pb) and indocyanine green (ICG); 2. a cocktail of albumin radiocolloids (99mTc-NanoColl), Pb, and ICG; or 3. a cocktail of radiolabeled albumin (99mTc-Vasculosis), Pb, and ICG. The distribution of these imaging agents over the lymph nodes (LNs) are studied at different time points after injection. We find that at 60-min postinjection, ICG significantly improves the detection of the LNs compared to Pb, 53 versus 7%, respectively. Moreover, a cocktail of ICG and 99mTc-NanoColl improves the fluorescent detection rate to 86%, equalling that of the clinically applied 99mTc-NanoColl. A similar overlap is observed in our initial clinical pilot data. Fluorescent detection of the LNs using a ICG with 99mTc-Vasculosis gives similar results as "free" ICG (58%; 60 min). A 99mTc-NanoColl, Pb, and cocktail ICG enriches the standard 99mTc-NanoColl approach by adding optical detection of the sentinel lymph nodes. Furthermore, this approach improves fluorescent-based guidance and enables both accurate surgical planning and intraoperative detection, based on a single injection.     

Volume CT with a flat-panel detector on a mobile, isocentric C-arm: pre-clinical investigation in guidance of minimally invasive surgery

A mobile isocentric C-arm (Siemens PowerMobil) has been modified in our laboratory to include a large area flat-panel detector (in place of the x-ray image intensifier), providing multi-mode fluoroscopy and cone-beam computed tomography (CT) imaging capability. This platform represents a promising technology for minimally invasive, image-guided surgical procedures where precision in the placement of interventional tools with respect to bony and soft-tissue structures is critical. The image quality and performance in surgical guidance was investigated in pre-clinical evaluation in image-guided spinal surgery. The control, acquisition, and reconstruction system are described. The reproducibility of geometric calibration, essential to achieving high three-dimensional (3D) image quality, is tested over extended time scales (7 months) and across a broad range in C-arm angulation (up to 45 degrees), quantifying the effect of improper calibration on spatial resolution, soft-tissue visibility, and image artifacts. Phantom studies were performed to investigate the precision of 3D localization (viz., fiber optic probes within a vertebral body) and effect of lateral projection truncation (limited field of view) on soft-tissue detectability in image reconstructions. Pre-clinical investigation was undertaken in a specific spinal procedure (photodynamic therapy of spinal metastases) in five animal subjects (pigs). In each procedure, placement of fiber optic catheters in two vertebrae (L1 and L2) was guided by fluoroscopy and cone-beam CT. Experience across five procedures is reported, focusing on 3D image quality, the effects of respiratory motion, limited field of view, reconstruction filter, and imaging dose. Overall, the intraoperative cone-beam CT images were sufficient for guidance of needles and catheters with respect to bony anatomy and improved surgical performance and confidence through 3D visualization and verification of transpedicular trajectories and tool placement. Future investigation includes improvement in image quality, particularly regarding x-ray scatter, motion artifacts and field of view, and integration with optical tracking and navigation systems.     

Toldt’s间隙的CT影像解剖学观察及临床意义

目的　术前通过CT影像识别Toldt’s间隙,为腹腔镜结直肠癌手术寻找正确的外科平面,从而制订具有前瞻性的个性化术式。 方法　通过对南方医科大学附属顺德第一人民医院2010年1月~2012年6月246例腹腔镜结直肠癌手术患者的术前CT影像及术中镜下所见对照观察,确认Toldt’s间隙的位置、沟通和毗邻关系。 结果　术前CT影像观察到:升降结肠系膜后叶与肾前筋膜融合成的线影即为Toldt’s线。结直肠癌术前CT所显示的Toldt’s筋膜间隙与术中所见具有较好的一致性(Kappa值为0.718)。腹腔镜结直肠癌手术时沿此线切开,以肾前筋膜为参照面,即可建立正确的外科平面。 结论　①术前CT影像可指导术中构建正确的Toldt’s间隙外科平面,保持肾前筋膜的完整性;②CT可提示肿瘤是否侵犯Toldt’s间隙平面,对于制订个性化术式和预后评估具有前瞻性意义。     

单光子发射型计算机断层成像与CT融合图像评价125I粒子在靶器官中的分布

目的 结合全身扫描,探讨单光子发射型计算机断层成像(SPECT)与CT融合图像对植入的放射性125I粒子在体内分布的评价.方法 2008年5月至2009年6月复旦大学附属中山医院核医学科接受治疗的47例125I粒子植入患者中,6例前列腺癌患者实施了超声诱导下125I粒子植入,另41例有明确肿瘤病史并伴有门静脉或上腔静脉癌栓患者,在数字减影血管成像(DSA)诱导下行支架和125I粒子链条植入到血管腔内.所有患者在125I粒子植入24 h后行全身扫描,再根据125I粒子所在部位行SPECT与CT显像检查.结合全身扫描图像和SPECT与CT图像对植入125I粒子的分布情况进行评价.结果 全身扫描图像为SPECT与CT检查提供准确定位,但无法显示粒子的准确解剖部位.6例前列腺癌患者中,SPECT与CT融合图像显示5例患者植入粒子在前列腺内分布较好,而1例患者粒子植入到右侧精囊腺内;41例有明确肿瘤病史并伴有门静脉或上腔静脉癌栓患者中,SPECT与CT融合图像显示40例血管腔内的粒子链条位于合理的位置,1例植入到上腔静脉内的粒子链条脱离到右心腔内.结论 结合全身扫描,SPECT与CT融合图像可以评价125I粒子在靶器官的分布情况,能及时发现位置偏离的粒子.     

单光子发射型计算机断层成像与CT融合图像评价^125I粒子在靶器官中的分布

目的结合全身扫描,探讨单光子发射型计算机断层成像（SPECT）与CT融合图像对植入的放射性^125I粒子在体内分布的评价。方法2008年5月至2009年6月复旦大学附属中山医院核医学科接受治疗的47例^125I粒子植入患者中,6例前列腺癌患者实施了超声诱导下^125I粒子植入,另41例有明确肿瘤病史并伴有门静脉或上腔静脉癌栓患者,在数字减影血管成像（DSA）诱导下行支架和^125I粒子链条植入到血管腔内。所有患者在^125I粒子植入24h后行全身扫描,再根据^125I粒子所在部位行SPECT与CT显像检查。结合全身扫描图像和SPECT与CT图像对植入^125I粒子的分布情况进行评价。结果全身扫描图像为SPECT与CT检查提供准确定位,但无法显示粒子的准确解剖部位。6例前列腺癌患者中,SPECT与CT融合图像显示5例患者植入粒子在前列腺内分布较好,而1例患者粒子植入到右侧精囊腺内;41例有明确肿瘤病史并伴有门静脉或上腔静脉癌栓患者中,SPECT与CT融合图像显示40例血管腔内的粒子链条位于合理的位置,1例植入到上腔静脉内的粒子链条脱离到右心腔内。结论结合全身扫描,SPECT与CT融合图像可以评价^125I粒子在靶器官的分布情况,能及时发现位置偏离的粒子。     

Subject-specific models for image-guided cardiac surgery

Three-dimensional visualization for planning and guidance is still not routinely available for minimally invasive cardiac surgery (MICS). This can be addressed by providing the surgeon with subject-specific geometric models derived from 3D preoperative images for planning of port locations or to rehearse the procedure. For guidance purposes, these models can also be registered to the subject using intraoperative images. In this paper, we present a method for extracting subject-specific heart geometry from preoperative MR images. The main obstacle we face is the low quality of clinical data in terms of resolution, signal-to-noise ratio, and presence of artefacts. Instead of using these images directly, we approach the problem in three steps: (1) generate a high quality template model, (2) register the template with the preoperative data, and (3) animate the result over the cardiac cycle. Validation of this approach showed that dynamic subject-specific models can be generated with a mean error of 3.6 +/- 1.1 mm from low resolution target images (6 mm slices). Thus, the models are sufficiently accurate for MICS training and procedure planning. In terms of guidance, we also demonstrate how the resulting models may be adapted to the operating room using intraoperative ultrasound imaging.     

2D to 3D fusion of echocardiography and cardiac CT for TAVR and TAVI image guidance

This study proposed a registration framework to fuse 2D echocardiography images of the aortic valve with preoperative cardiac CT volume. The registration facilitates the fusion of CT and echocardiography to aid the diagnosis of aortic valve diseases and provide surgical guidance during transcatheter aortic valve replacement and implantation. The image registration framework consists of two major steps: temporal synchronization and spatial registration. Temporal synchronization allows time stamping of echocardiography time series data to identify frames that are at similar cardiac phase as the CT volume. Spatial registration is an intensity-based normalized mutual information method applied with pattern search optimization algorithm to produce an interpolated cardiac CT image that matches the echocardiography image. Our proposed registration method has been applied on the short-axis “Mercedes Benz” sign view of the aortic valve and long-axis parasternal view of echocardiography images from ten patients. The accuracy of our fully automated registration method was 0.81 ± 0.08 and 1.30 ± 0.13 mm in terms of Dice coefficient and Hausdorff distance for short-axis aortic valve view registration, whereas for long-axis parasternal view registration it was 0.79 ± 0.02 and 1.19 ± 0.11 mm, respectively. This accuracy is comparable to gold standard manual registration by expert. There was no significant difference in aortic annulus diameter measurement between the automatically and manually registered CT images. Without the use of optical tracking, we have shown the applicability of this technique for effective fusion of echocardiography with preoperative CT volume to potentially facilitate catheter-based surgery.     

Application of soft tissue modelling to image-guided surgery

The deformation of soft tissue compromises the accuracy of image-guided surgery based on preoperative images, and restricts its applicability to surgery on or near bony structures. One way to overcome these limitations is to combine biomechanical models with sparse intraoperative data, in order to realistically warp the preoperative image to match the surgical situation. We detail the process of biomechanical modelling in the context of image-guided surgery. We focus in particular on the finite element method, which is shown to be a promising approach, and review the constitutive relationships which have been suggested for representing tissue during surgery. Appropriate intraoperative measurements are required to constrain the deformation, and we discuss the potential of the modalities which have been applied to this task. This technology is on the verge of transition into clinical practice, where it promises to increase the guidance accuracy and facilitate less invasive interventions. We describe here how soft tissue modelling techniques have been applied to image-guided surgery applications.     

Brain shift compensation and neurosurgical image fusion using intraoperative MRI: current status and future challenges

Navigation systems are commonly used in neurosurgical operating theaters. Generally, they either rely on the use of preoperative or intraoperative image data. Using preoperative image data, the phenomenon of brain shift contributes most to errors, in addition to various other sources of decreased reliability, such as image-related errors or registration inaccuracy. Updating navigation after intraoperative magnetic resonance imaging (iMRI) serves as immediate feedback on the surgical result and furthermore compensates for the effects of brain shift. Together with an integration of functional data in the navigation such as diffusion tensor imaging (DTI)-based fiber tracking or functional MRI, there is evidence that iMRI contributes to maximize extent of resection in glioma surgery with a preservation of neurological function. The following article summarizes the work flow and clinical impact of iMRI and functional navigation, as well as current problems and possible solutions.     

Wearable Mixed-Reality Holographic Navigation Guiding the Management of Penetrating Intracranial Injury Caused by a Nail

Penetrating brain injury caused by a nail is an extremely rare neurosurgical emergency that poses a challenge for neurosurgeons. Nail entering the brain from the orbit and lodging within the cranial cavity is even more unusual. A 53-year-old male was found unconscious at a construction site, and brain CT revealed not only the presence of a nail beneath the inner table of the parietal bone, but also traumatic intracerebral hematoma. Consequently, accurate localization of the nail and hematoma was mandatory for surgical plan. During surgical planning, computational model reconstruction and trajectory calculation were completed using preoperative CT in 3D Slicer. Under the guidance of a head-mounted mixed-reality holographic computer, the neurosurgeon was able to visualize and interact with the hologram of the surgical plan, and intraoperative findings demonstrated that our low-cost portable wearable mixed-reality holographic navigation assisted precise localization of the nail and intracerebral hematoma, assuring less injury to the already compromised brain. After the surgery, the patient could obey commands, and postoperative imaging ruled out the possibility of brain abscess during follow-up. To the best of our knowledge, this is the first report on using a low-cost wearable mixed-reality holographic navigation to guide the management of penetrating intracranial injury caused by a nail.     

计算机导航辅助下切除四肢干骺端恶性肿瘤保留自体关节的安全性及长期随访疗效评估

目的 探讨计算机导航辅助下切除四肢干骺端恶性肿瘤保留自体关节的安全性及长期随访疗效。方法 选择2007年1月至2011年9月10例四肢关节干骺端IIB期恶性肿瘤患者,其中7例骨肉瘤,3例尤文肉瘤。术前薄层CT扫描数据和MRI数据输入计算机导航系统进行图像融合,术中用导航探头经过导航跟踪器将手术部位和导航计算机建立联系,然后用导航探头在固定的解剖定位点或术前制作的人工标记点进行计算机注册,再在骨暴露表面散在选择50个点注册增加图像和手术部位配准的准确性,验证若匹配误差小于1 mm则可用于术中导航。然后在导航指导下精准截骨切除肿瘤,腓骨瓣复合异体骨重建肿瘤切除后的骨缺损,术后定期随访,评估保留关节功能、有无肿瘤局部复发及相关并发症等。结果 术中计算机导航匹配误差平均为0.41 mm,导航下截骨线与肿瘤边缘之间的平均距离为9.9 mm,术后平均随访140个月,除1例肿瘤肺转移死亡外,其余所有患者均无瘤存活,所有患者均无局部肿瘤复发,肢体MSTS评分平均为27.8分。结论 导航辅助下可做到肿瘤精确切除,使关节结构保留最大化的同时保证肿瘤不复发,而保留的自体关节使得患者可以长期使用。     

Registration accuracy enhancement of a surgical navigation system for anterior cruciate ligament reconstruction: A phantom and cadaveric study

Background

Recently, surgical navigation systems have been widely used to improve the results of various orthopaedic surgeries. However, surgical navigation has not been successful in anterior cruciate ligament reconstruction, owing to its inaccuracy and inconvenience. This study investigated the registration of preoperative and intraoperative data, which are the key components in improving accuracy of the navigation system.

Tumor bracketing and safety margin estimation using multimodal marker seeds: a proof of concept

Accurate tumor excision is crucial in the locoregional treatment of cancer, and for this purpose, surgeons often rely on guide wires or radioactive markers for guidance toward the lesion. Further improvement may be obtained by adding optical guidance to currently used methods, in the form of intra-operative fluorescence imaging. To achieve such a multimodal approach, we have generated markers that can be used in a pre-, intra-, and post-operative setting, based on a cocktail of a dual-emissive inorganic dye, lipids, and pertechnetate. Phantom experiments demonstrate that these seeds can be placed accurately around a surrogate tumor using ultrasound. Three-dimensional bracketing provides delineation of the entire lesion. Combined with the multimodal nature, this provides the opportunity to predetermine the resection margins by validating the placement accuracy using multiple imaging modalities (namely, x ray, MRI, SPECT/CT, and ultrasound). The dual-emissive fluorescent properties of the dye provide the unique opportunity to intra-operatively estimate the depth of the seed in the tissue via multispectral imaging: emission green λmax=520 nm≤5 mm penetration versus emission red λmax=660 nm≤12 mm penetration. By using particles with different colors, the original geographic orientation of the excised tissue can be determined.     

Computer-aided oral implantology: methods and applications

Aiming at transferring the preoperative planning information to the patient in oral implantology, this study presents an image guided oral implant system (IGOIS), which integrates 3D medical modelling, preoperative surgical planning and intraoperative tracking into a dental navigation system. With the fabrication of a tooth-supported polymer resin template, a non-invasive point-based registration method through ICP algorithm is explicitly discussed. The experimental test shows that deviation between planned and achieved position of the implant is 1.2 mm at the tip and 1.3 mm at the head, which thereby demonstrates that IGOIS can reach a level of accuracy where further clinical developments are feasible.     

Computer-aided oral implantology: methods and applications

Aiming at transferring the preoperative planning information to the patient in oral implantology, this study presents an image guided oral implant system (IGOIS), which integrates 3D medical modelling, preoperative surgical planning and intraoperative tracking into a dental navigation system. With the fabrication of a tooth-supported polymer resin template, a non-invasive point-based registration method through ICP algorithm is explicitly discussed. The experimental test shows that deviation between planned and achieved position of the implant is 1.2 mm at the tip and 1.3 mm at the head, which thereby demonstrates that IGOIS can reach a level of accuracy where further clinical developments are feasible.     

Computer-enhanced stereoscopic vision in a head-mounted operating binocular

Based on the Varioscope, a commercially available head-mounted operating binocular, we have developed the Varioscope AR, a see through head-mounted display (HMD) for augmented reality visualization that seamlessly fits into the infrastructure of a surgical navigation system. We have assessed the extent to which stereoscopic visualization improves target localization in computer-aided surgery in a phantom study. In order to quantify the depth perception of a user aiming at a given target, we have designed a phantom simulating typical clinical situations in skull base surgery. Sixteen steel spheres were fixed at the base of a bony skull, and several typical craniotomies were applied. After having taken CT scans, the skull was filled with opaque jelly in order to simulate brain tissue. The positions of the spheres were registered using VISIT, a system for computer-aided surgical navigation. Then attempts were made to locate the steel spheres with a bayonet probe through the craniotomies using VISIT and the Varioscope AR as a stereoscopic display device. Localization of targets 4 mm in diameter using stereoscopic vision and additional visual cues indicating target proximity had a success rate (defined as a first-trial hit rate) of 87.5%. Using monoscopic vision and target proximity indication, the success rate was found to be 66.6%. Omission of visual hints on reaching a target yielded a success rate of 79.2% in the stereo case and 56.25% with monoscopic vision. Time requirements for localizing all 16 targets ranged from 7.5 min (stereo, with proximity cues) to 10 min (mono, without proximity cues). Navigation error is primarily governed by the accuracy of registration in the navigation system, whereas the HMD does not appear to influence localization significantly. We conclude that stereo vision is a valuable tool in augmented reality guided interventions.     

虚拟内窥镜图像增强膝关节镜手术导航系统

膝关节镜手术是利用内窥镜的膝关节微创手术,具有创口小、恢复快等优势,但同时整个手术仅凭术中二维膝关节镜图像引导,存在缺乏深度信息、容易出现遮挡、依赖手术经验等缺点。利用虚拟内窥镜技术,将术前与术中的信息结合,互为补充,为膝关节镜手术进行导航,增加其便利性和可靠性。提出基于虚拟内窥镜技术的膝关节镜手术导航系统:首先通过对内窥镜及整个坐标系统的标定,完成对整个系统的坐标描述;然后针对实时追踪的内窥镜视角,实现对应范围术前信息的渲染,最后将术前术中及融合信息通过二维、三维显示方式,全面地展示给医师。完成系统的搭建及完整的膝关节模型实验,将术前术中信息同时显示、精确融合,实现导航功能;实验的定位标定均方误差小于1 mm,术前术中图像融合匹配均方误差小于0.7 mm,分立及融合图像均可实时显示。综合定位信息与术前信息的膝关节镜手术导航系统,可以实时进行内窥镜图像增强,为膝关节镜术提供多源信息融合引导,为医生提供直观、便捷的手术导航效果。