影像组学在结直肠癌肝转移诊疗中的应用进展

结直肠癌发病率呈逐年上升趋势,肝脏是其远处转移最常见的靶器官。目前传统影像学在发现结直肠癌隐匿性肝转移灶、预测异时性肝转移及评估治疗反应方面仍有不足。影像组学可从医学图像数据中挖掘并提取肉眼难以分辨的信息,反映肿瘤内部异质性特征,从而为结直肠癌肝转移的预测、诊断、疗效评估及预后判断提供更多的辅助信息。就影像组学在结直肠癌肝转移诊疗中的应用进展进行综述。     

Radio-frequency ablation of colorectal liver metastases in 167 patients

The objective of this paper is to report our results from a prospective study of 167 patients with colorectal liver metastases treated with radio-frequency ablation (RFA). Three hundred fifty-four treatments were performed in 167 patients, 99 males, mean age 57 years (34–87). The mean number of metastases was 4.1 (1–27). The mean maximum diameter was 3.9 cm (1–12). Fifty-one (31%) had stable/treated extra-hepatic disease. Treatments were performed under general anaesthesia using US and CT guidance and single or cluster water-cooled electrodes (Valleylab, Boulder, CO). All patients had been rejected for or had refused surgical resection. Eighty percent received chemotherapy. Survival data were stratified by tumour burden at the time of first RFA. The mean number of RFA treatments was 2.1 (1–7). During a mean follow-up of 17 months (0–89), 72 developed new liver metastases and 71 developed progressive extra-hepatic disease. There were 14/354 (4%) major local complications and 22/354 (6%) minor local complications. For patients with 5 metastases, maximum diameter 5 cm and no extra-hepatic disease, the 5-year survival from the time of diagnosis was 30% and from the time of first thermal ablation was 26%. Given that the 5-year survival for operable patients is a median of 32%, our 5-year survival of 30% is promising.     

Small colorectal liver metastases: Detection with SPIO-enhanced MRI in comparison with gadobenate dimeglumine-enhanced MRI and CT imaging

The aim of this prospective study was to compare the diagnostic role of superparamagnetic iron oxide (SPIO)-enhanced liver magnetic resonance imaging (MRI) versus gadobenate dimeglumine (GbD)-enhanced MRI and computed tomography (CT) investigations for detection of small (less than 1 cm) colorectal liver metastases (LMs) of colorectal cancer. Seventy-eight LMs in 16 patients were evaluated with dynamic CT imaging, GbD-enhanced dynamic MR imaging and SPIO-enhanced MR imaging. Two radiologists were reviewed the LMs seperately. Agreement between the readers and three algorithms was analyzed. Differences between the lesion detection ratios of the methods were analyzed by two proportion z test. Sensitivity values of each modality were also calculated. Interobserver agreement values with kappa analysis were found to be the best for three modalities and kappa values were 0.866, 0.843, and 1.0 respectively. For all 78 LMs, SPIO-enhanced MRI detected all lesions (100% sensitivity). This sensitivity value was higher than GbD-enhanced MRI, and there was a significant difference (p < 0.05). GbD-enhanced MRI depicted 71 lesions and this modality could not detected 7 lesions (91% sensitivity). This modality had moderate sensitivity, and this value is greater than CT imaging, so there was a significant difference also (p < 0.05). Dynamic triphasic CT imaging detected 64 (R1) and 65 (R2) LMs. This modality had the lowest sensitivity (R1: 0.82, R2: 0.83 respectively). Only SPIO-enhanced MRI was able to detect all LMs less than 1 cm. LMs were the best detected with SPIO-enhanced MRI. We recommend SPIO-enhanced MRI to be the primary alternative modality especially for diagnosis of small colorectal LMs.     

Response assessment of colorectal liver metastases with contrast enhanced CT/18F-FDG PET

Purpose

Evaluate the diagnostic performance of contrast enhanced CT/PET (ceCT/PET) in the response assessment of patients with colorectal cancer liver metastases.

Methods

33 ce CT/PET studies of 19 patients with colorectal liver metastases were prospectively evaluated. All of them, 13 (68.4%) were males and 6 (31.6%) females. Mean age and range were 63 [42–78]. All patients were treated with neoadjuvant chemotherapy. In all cases post-therapy diagnostic confirmation of liver lesions was obtained. A ce CT PET/was obtained 1 h after the injection of 370 MBq of 18F-FDG.Metabolic and morphologic studies were evaluated by two blinded nuclear physicians and radiologists respectively to assess the location, size and suspected diagnosis of lesions (benign or malignant). A combined assessment of both techniques was performed.The final diagnosis was established by histopathology or clinical/radiological follow-up greater than 6 months.

Results

A total of 120 liver lesions were identified, 115 were malignant and 5 benign.From the malignant lesions, 105 were identified with the ceCT, 44 with the PET and 109 with ceCT/PET. All of the benign lesions were correctly classified with any of the three imaging techniques.The sensitivity of PET, ceCT and ceCT/PET were of 38%, 91% and 95% respectively and the specificity was 100% in all three of the diagnostic studies.

Conclusion

Administration of intravenous contrast in the PET/CT is mandatory to evaluate treatment response rate of liver metastases due to the limitations of isolated metabolic images in these cases.     

Comparison of FDG-PET, PET/CT and MRI for follow-up of colorectal liver metastases treated with radiofrequency ablation: initial results

PURPOSE: Morphologic imaging after radiofrequency ablation (RFA) of liver metastases is hampered by rim-like enhancement in the ablation margin, making the identification of local tumor progression (LTP) difficult. Follow-up with PET/CT is compared to follow-up with PET alone and MRI after RFA. METHODS AND MATERIALS: Sixteen patients showed 25 FDG-positive colorectal liver metastases in pre-interventional PET/CT. Post-interventional PET/CT was performed 24h after ablation and was repeated after 1, 3 and 6 months and then every 6 months. PET and PET/CT data were compared with MR data sets acquired within 14 days before or after these time points. Either histological proof by biopsy or resection, or a combination of contrast-enhanced CT at fixed time points and clinical data served as a reference. RESULTS: The 25 metastases showed a mean size of 20mm and were treated with 39 RFA sessions. Ten lesions which developed LTP received a second round of RFA; four lesions received three rounds of treatment. The mean follow-up time was 22 months. Seventy-two PET/CT and 57 MR examinations were performed for follow-up. The accuracy and sensitivity for tumor detection was 86% and 76% for PET alone, 91% and 83% for PET/CT and 92% and 75% for MRI, respectively. CONCLUSIONS: In comparison to PET alone, PET/CT was significantly better for detecting LTP after RFA. There were no significant differences between MRI and PET/CT. These preliminary results, however, need further verification.     

扩散加权成像联合钆塞酸二钠增强MRI在肝转移瘤诊断中的研究进展

早期检出肝脏转移瘤对选择合适的治疗方案和提高病人术后生存率有较大价值。扩散加权成像主要反映活体组织中水分子的布朗运动,在肝脏局灶性病变的检出和定性方面显示出较大优势,尤其是在肝脏微小转移瘤的检出方面;而钆塞酸二钠(Gd-EOB-DTPA)增强MRI是一种既能进行肝脏动态增强扫描又能提供肝脏特异性信息的影像检查方法,在肝脏转移瘤检出方面的价值和准确性均较高。就DWI联合Gd-EOB-DTPA增强MRI在肝脏转移瘤检出中的研究进展予以综述。     

Detection of colorectal hepatic metastases using MnDPDP MR imaging and diffusion-weighted imaging (DWI) alone and in combination

To compare the diagnostic accuracy of MnDPDP MR imaging and diffusion-weighted imaging (DWI), alone and in combination, for detecting colorectal liver metastases in patients with suspected metastatic disease. Thirty-three consecutive patients with suspected colorectal liver metastases underwent MR imaging. Three image sets (MnDPDP, DWI and combined MnDPDP and DWI) were reviewed independently by two observers. Lesions were scored on a five-point scale for malignancy and the areas (Az) under the receiver operating characteristic curves were calculated for each observer and image set. The sensitivity and specificity for lesion detection were calculated for each image set and compared. There were 83 metastases, 49 cysts and 1 haemangioma. Using the combined set resulted in the highest diagnostic accuracy for both observers (Az = 0.94 and 0.96), with improved averaged sensitivity of lesion detection compared with the DWI set (p = 0.01), and a trend towards improved sensitivity compared with the MnDPDP set (p = 0.06). There was no difference in the averaged specificity using any of the three image sets (p > 0.5). Combination of MnDPDP MR imaging and DWI resulted in the highest diagnostic accuracy and can increase sensitivity without loss in specificity.     

Subtraction-multiphase-CT unbeneficial for early detection of colorectal liver metastases

Purpose

To assess the value of multiphase-subtraction-CT for early detection of colorectal-liver-metastases (CRLM).

Methods and materials

In 50 patients suspected of CRLM a routine pre-operative 4-phase-CT-scan of the upper abdomen was obtained. All 12 possible image subtractions between two different phases were constructed applying 3D-image-registration to decrease distortion artefacts induced by differences in inspiration volume. Two experienced radiologists initially reviewed the conventional 4-phase-CT for malignant and/or benign appearing lesions and at least 1-month hereafter the same 4-phase-CT now including the subtracted images. The results were compared to histology reports or to a combination of surgical exploration and intraoperative ultrasound together with results from pre-operative PET and follow-up examinations.

Results

Although an additional number of 31 malignant appearing lesions were detected on the subtraction images, none proved to represent a true CRLM. Interobserver agreement (κ) decreased from 0.627 (good) to 0.418 (fair).

Conclusion

Adding linearly co-registered subtraction-CT images to a conventional 4-phase-CT protocol does not improve detection of CRLM.     

胃、结（直）肠癌肝转移的介入治疗（附55例报告）

目的 评价胃、结(直)肠癌肝转移瘤介入治疗效果及影响因素。方法采用Seldinger法经股动脉插管,治疗胃癌、结(直)肠癌肝转移21例、34例。化疗药物选择5一Fu、PDD、ADM或ADM与碘化油乳剂作栓塞治疗。结果(1)胃、结(直)肠癌肝转移瘤总有效率(CR PR)为64％;(2)34例转移瘤碘化油沉积CT分为四型：均匀型占20％,非均匀型占39％,环型占9％,无碘油沉积型占32％;(3)转移瘤疗效最好为单发、多血供病灶及均匀碘化油蓄积;(4)64％病例治疗后出现肝外转移。结论介入化疗栓塞治疗为胃、结(直)肠癌肝转移有效的姑息治疗手段。     

立体定向放射治疗在结直肠癌肝转移中的临床应用

目的 评价立体定向放射治疗（SBRT）在结直肠癌肝转移（CLM）中的治疗效果,为合理选择治疗手段提供依据。方法 解放军306医院收治的28例患者,包括男17例,女11例,中位年龄63.8岁（31~86岁）,共计54个病灶,行立体定向放射治疗。平静呼吸状态下的CT增强扫描影像分别进行大体肿瘤体积（GTV）、临床靶区体积（CTV）和计划靶区体积（PTV）的勾画,CTV为GTV外放5 mm,GTV为CTV外放5~10 mm。以50%~60%等剂量曲线作为处方剂量曲线,单次3~6 Gy,总剂量39~45 Gy,等效生物剂量50.7~65.3 Gy。治疗后3个月开始复查,以增强CT或MR显示的病灶体积的变化做为评价疗效的依据。根据RTOG毒性诊断标准对不良反应进行诊断和分级,比较局控率和生存率。结果 所有患者均顺利完成治疗,中位随访时间为15.1个月（3~30个月）,随访终点有7例患者存活。局控率为79.2%,1年和2年的总生存率分别为82.7%和48.6%。病灶体积与局控率关系密切,当体积小于14 cm³时,肿瘤局控率明显高于病灶体积大于65 cm³时（χ² = 4.17,P<0.05）。病灶体积大于180 cm³时,肿瘤局控率为零。不良反应包括治疗后乏力（60.7%）,1、2级消化道反应（28.6%）,一过性1、2级骨髓抑制（46.4%）,一过性转氨酶增高（17.8%）。全组未发生3级以上及晚期不良反应。结论 立体定向放射治疗可做为选择性病例尤其是不能手术的结直肠癌肝转移患者的首选局部治疗手段。     

Detection and classification of focal liver lesions in patients with colorectal cancer: retrospective comparison of diffusion-weighted MR imaging and multi-slice CT

Objectives

To compare the diagnostic performance of diffusion-weighted MR imaging (DWI) with multi-slice CT (MS-CT) in the detection and classification of focal liver lesions in patients with colorectal cancer.

Methods

In a retrospective study 68 patients who underwent DWI at 1.5 T (b-values of 50, 300 and 600 s/mm²) and contrast-enhanced MS-CT were analysed by two radiologists blinded to the clinical results. Imaging results were correlated with intraoperative surgical and ultrasound findings (n = 24), imaging follow-up or PET (n = 44). Sensitivity of DWI and MS-CT in detection of focal liver lesions was compared on a per-lesion and a per-segment basis. Receiver operator-characteristic (ROC) curves to determine the diagnostic performance and the sensitivities of correctly identifying liver metastases on a segmental base were calculated.

Results

For lesion detection, DWI was significantly superior to MS-CT both on a per-lesion (difference in sensitivities for reader 1 and 2 22.65% and 19.06%, p < 0.0001) and a per-segment basis (16.86% and 11.76%, p < 0.0001). Especially lesions smaller than 10 mm were better detected with DWI compared to MS-CT (difference 41.10% and 29.45%, p < 0.0001). ROC-analysis showed superiority for lesions classification (p < 0.0001) of DWI (AUC: 0.949 and 0.951) as compared to MS-CT (AUC: 0.879 and 0.892, p < 0.0001 and p = 0.005). DWI was able to filter out metastatic segments with a higher sensitivity (88.2 and 86.5%) compared to MS-CT (68.0 and 67.4%, p < 0.0001 and p = 0.005, respectively).

Conclusion

Compared to MS-CT DWI is both more sensitive in the detection of liver lesions and more accurate in determining the extent of metastatic disease in patients with colorectal cancer and therefore might help to optimize therapeutic management in those patients.     

Comparison of gadoxetic acid-enhanced dynamic imaging and diffusion-weighted imaging for the preoperative evaluation of colorectal liver metastases

Purpose:

To retrospectively compare the diagnostic accuracy for the detection of colorectal liver metastases between gadoxetic acid‐enhanced MRI (EOB‐MRI) and diffusion‐weighted imaging (DWI) on 3.0 Tesla (T) system, and then to determine whether a combination of the two techniques may improve the diagnostic performance.

Materials and Methods:

Forty‐seven patients underwent MR imaging at 3.0T, including DWI (DWI set) and dynamic and hepatobiliary phase EOB‐MRI (EOB set) for the preoperative evaluation of colorectal liver metastases. All suspicious metastases were confirmed by hepatic surgery. Two blinded readers independently reviewed three different image sets, which consisted of DWI set, EOB set, and combined set. The accuracy was assessed by the area (Az) under the alternative‐free response receiver operating characteristic curve, and the sensitivity and positive predictive value (PPV) were calculated.

Results:

We found a total of 78 confirmed colorectal liver metastases in 42 of 47 patients. Each reader noted higher diagnostic accuracy of combined set of EOB‐MRI and DWI than DWI set and EOB set, without statistical significance. Regardless of the size of colorectal liver metastasis, each reader detected significantly more metastases on combined set than on DWI set, and PPV was significantly higher with DWI set than with EOB set or with combined set for one reader.

Conclusion:

EOB‐MRI was more useful for the detection of colorectal liver metastases, while DWI was more useful for their characterization. The combination of EOB‐MRI and DWI showed significantly higher accuracy and sensitivity for the preoperative detection of small colorectal liver metastases than DWI. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Planning transarterial radioembolization of colorectal liver metastases with Yttrium 90 microspheres: evaluation of a sequential diagnostic approach using radiologic and nuclear medicine imaging techniques

The purpose of the study was to establish a diagnostic approach to the preparation of patients with colorectal liver metastases considered for transarterial radioembolization (RE). Twenty-two patients sequentially underwent computed tomography (CT; thorax/abdomen), magnetic resonance imaging (MRI; liver; hepatocyte-specific contrast), positron emission tomography (PET/PET-CT; F18-fluoro-desoxy-glucose), and angiography with perfusion scintigraphy [planar imaging; tomography with integrated CT (SPECT-CT)]. The algorithm was continued when no contraindication or alternative treatment option was found. The impact of each test on the therapy decision and RE management was recorded. Patient evaluation using CT revealed contraindications for RE in 4/22 patients (18%). Of the remaining 18 patients, 2 were excluded and 3 were assigned to locally ablative treatment based on MRI and PET results (28%). The remaining 13 patients entered the planning algorithm: SPECT-CT revealed gastrointestinal tracer accumulations in 4 (31%) patients [SPECT, 2 (15%)], making a modified application necessary. In five patients (38%), planar scintigraphy revealed relevant hepatopulmonary shunting. Therapy was finally administered to all 13 patients without therapy-related pulmonary or gastrointestinal morbidity. Each part of the diagnostic algorithm showed a relevant impact on patient management. The sequential approach appears to be suitable and keeps the number of unnecessary treatments and therapy risks to a minimum.     

Accuracy and confidence of Gd-EOB-DTPA enhanced MRI and diffusion-weighted imaging alone and in combination for the diagnosis of liver metastases

Purpose

To evaluate the accuracy and confidence in diagnosing liver metastases using combined gadolinium-EOB-DTPA (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI)/diffusion-weighted imaging (DWI) in comparison to Gd-EOB-DTPA enhanced MRI and DWI alone.

Materials and methods

Forty-three patients (age, 58 ± 13 years) with 89 liver lesions (28 benign, 61 malignant) underwent liver MRI for suspected liver metastases. Three image sets (DWI, Gd-EOB-DTPA and combined Gd-EOB-DTPA/DWI) in combination with unenhanced T1- and T2-weighted images were reviewed by three readers. Detection rates of focal liver lesions were assessed and diagnostic accuracy was evaluated by calculating the areas under the receiver-operating-characteristics curve (AUC). Confidence in diagnosis was evaluated on a 3-point scale. Histopathology and imaging follow-up served as the standard of reference.

Results

Detection of liver lesions and confidence in final diagnosis for all readers were significantly higher for the combined Gd-EOB-DTPA/DWI dataset than for DWI. The combination of DWI and Gd-EOB-DTPA rendered a significantly higher confidence in final diagnosis (2.44 vs. 2.50) than Gd-EOB-DTPA alone for one reader. For two readers, accuracy in diagnosis of liver metastases was significantly higher for Gd-EOB-DTPA/DWI (AUCs of 0.84 and 0.83) than for DWI datasets (AUCs of 0.73 and 0.72). Adding DWI to Gd-EOB-DTPA did not significantly increase diagnostic accuracy as compared to Gd-EOB-DTPA imaging alone.

Conclusion

Addition of DWI sequences to Gd-EOB-DTPA enhanced MRI did not significantly increase diagnostic accuracy as compared to Gd-EOB-DTPA enhanced MRI alone in the diagnosis of liver metastases. However, the increase in diagnostic confidence might justify acquisition of DWI sequences in a dedicated MRI protocol.     

肝动脉内持续灌注治疗结直肠癌术后肝转移瘤

目的：探讨5－氟尿嘧啶（5－Fu)／甲酰四氢叶酸钙（CF）经肝动脉持续性灌注治疗结直肠癌肝转移的临床疗效。方法：62例无外科手术指征的结直肠癌肝转移患者，其原发病灶均已作根除术，依据肝动脉内化疗方式不同分为2组：A组32例，采取经皮肝动脉内植入药盒，术后经药盒每个月连续5d持续灌注5－Fu／CF及地塞米松；B组30例，采取每个月1次肝动脉插管大剂量灌注5－Fu/CF。结果：A，B组有效率（完全缓解＋部分缓解）分别为50．0％和23．3％（P＜0．05）。A组1年，2年生率分别为65．6%，39．3％，B组分别为36．7％，11．5％（P＜0．05）。A组1年，2年生存率分别为65．6％，39．3％，B组分别为36．7％，11．5％（P＜0．05）。A组生存质量明显改善，肝，胆，胃十二指肠毒性均较B组低。结论：经药盒肝动脉持续性灌注5－Fu/CF并配合地塞米松治疗结直肠癌肝转移可明显改善患者生存质量，提高生存率。     

Size determination and response assessment of liver metastases with computed tomography—Comparison of RECIST and volumetric algorithms

Objective

To compare different three-dimensional volumetric algorithms (3D-algorithms) and RECIST for size measurement and response assessment in liver metastases from colorectal and pancreatic cancer.

Methods

The volumes of a total of 102 liver metastases in 45 patients (pancreatic cancer, n = 22; colon cancer, n = 23) were estimated using three volumetric methods (seeded region growing method, slice-based segmentation, threshold-based segmentation) and the RECIST 1.1 method with volume calculation based on the largest axial diameter. Each measurement was performed three times by one observer. All four methods were applied to follow-up on 55 liver metastases in 29 patients undergoing systemic treatment (median follow-up, 3.5 months; range, 1–10 months). Analysis of variance (ANOVA) with post hoc tests was performed to analyze intraobserver variability and intermethod differences.

Results

ANOVA showed significant higher volumes calculated according to the RECIST guideline compared to the other measurement methods (p < 0.001) with relative differences ranging from 0.4% to 41.1%. Intraobserver variability was significantly higher (p < 0.001) for RECIST and threshold based segmentation (3.6–32.8%) compared with slice segmentation (0.4–13.7%) and seeded region growing method (0.6–10.8%). In the follow-up study, the 3D-algorithms and the assessment following RECIST 1.1 showed a discordant classification of treatment response in 10–21% of the patients.

Conclusions

This study supports the use of volumetric measurement methods due to significant higher intraobserver reproducibility compared to RECIST. Substantial discrepancies in tumor response classification between RECIST and volumetric methods depending on applied thresholds confirm the requirement of a consensus concerning volumetric criteria for response assessment.     

Prediction and monitoring of treatment effect using T1-weighted dynamic contrast-enhanced magnetic resonance imaging in colorectal liver metastases: Potential of whole tumour ROI and selective ROI analysis

Purpose

To evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for prediction and early monitoring of treatment in colorectal liver metastases.

Materials and methods

Ten patients were included. Baseline and follow-up DCE-MRI examinations were evaluated by whole tumour and selected ROI placements calculating Kep-values. Selective ROIs, concentric-like and hot spot, were drawn on early arterial phase images. Monitoring of treatment was performed comparing RECIST1.1 criteria with whole tumour and selected ROI placement. To evaluate treatment effect between responders and non-responders, independent samples t-test was used on Kep-values.

Results

In each patient largest lesion was evaluated totalling 10 target lesions. At baseline, for whole tumour ROI placements mean Kep-values in responders were significantly higher than mean Kep-values in non-responders (t = 7.481, p < 0.001). Selective ROI placement comparison of mean Kep-values at baseline and after 6 weeks of treatment (first follow-up measurement) showed significant decrease in responding patients (t = 4.706, p = 0.003) whereas increase in Kep-values in non-responding patients was not statistically significant.

Conclusion

This preliminary study shows that baseline Kep for whole tumour ROI is a predictor for treatment outcome. Decrease of Kep using selective ROIs allows early identification of response after 6 weeks of treatment.     

Additional value of contrast enhanced intraoperative ultrasound for colorectal liver metastases

BACKGROUND: Substantial recurrence rates following partial liver resection for colorectal liver metastases (CRM) imply that small metastases remain undetected using intraoperative ultrasound (IOUS). The aim of this study was to evaluate the additional value of contrast enhanced IOUS (CE-IOUS) when compared to preoperative contrast enhanced computed tomography (CE-CT) and IOUS in liver surgery for CRM. METHODS: After obtaining informed consent, 39 consecutive patients with CRM were included prospectively for evaluation. The study population consisted of 26 male and 13 female patients with a median (range) age of 62 (49-83) years. A lesion-per-lesion analysis was performed with histopathological examination as the reference standard after resection and follow-up for unresected lesions. The added value of CE-IOUS in correctly diagnosing malignant lesions was statistically evaluated, using receiver operating characteristic curves. RESULTS: A total of 234 lesions were identified, 137 of which were malignant, according to the reference standard. The addition of CE-IOUS did not improve the diagnostic accuracy when compared to the combination of CE-CT and IOUS (P=0.617). In one of two patients with newly detected lesions on CE-IOUS the extent of resection changed. CONCLUSIONS: The addition of CE-IOUS to preoperative CE-CT and IOUS does not improve the ability to characterize already detected lesions. In a small number of patients it appears to facilitate the detection of new metastatic lesions with implications on surgical strategy.