This article reviews the clinical applications of Superb Microvascular Imaging (SMI; Canon Medical Systems, Otawara, Japan) in the liver, breast, thyroid, skeletal muscle, and carotid plaques. Diseases that are closely associated with angiogenesis can be diagnosed by SMI in a relatively early phase, and using SMI can prevent adverse reactions associated with the contrast agents used in contrast-enhanced ultrasound. Super Microvascular Imaging also shows particular value in grading disease activities and monitoring therapeutic responses. Although SMI has some limitations, such as a lack of clinical standards, it can add information to conventional ultrasound examinations and may become a noninvasive alternative to invasive diagnostic procedures for many clinical conditions.

Clinical Applications of Superb Microvascular Imaging in the Liver, Breast, Thyroid, Skeletal Muscle, and Carotid Plaques.

To develop a supervised machine learning (ML) algorithm predicting above- versus below-median overall survival (OS) from diffusion-weighted imaging-derived radiomic features in patients with pancreatic ductal adenocarcinoma (PDAC). One hundred two patients with histopathologically proven PDAC were retrospectively assessed as training cohort, and 30 prospectively accrued and retrospectively enrolled patients served as independent validation cohort (IVC). Tumors were segmented on preoperative apparent diffusion coefficient (ADC) maps, and radiomic features were extracted. A random forest ML algorithm was fit to the training cohort and tested in the IVC. Histopathological subtype of tumor samples was assessed by immunohistochemistry in 21 IVC patients. Individual radiomic feature importance was evaluated by assessment of tree node Gini impurity decrease and recursive feature elimination. Fisher’s exact test, 95% confidence intervals (CI), and receiver operating characteristic area under the curve (ROC-AUC) were used. The ML algorithm achieved 87% sensitivity (95% IC 67.3–92.7), 80% specificity (95% CI 74.0–86.7), and ROC-AUC 90% for the prediction of above- versus below-median OS in the IVC. Heterogeneity-related features were highly ranked by the model. Of the 21 patients with determined histopathological subtype, 8/9 patients predicted to experience below-median OS exhibited the quasi-mesenchymal subtype, whilst 11/12 patients predicted to experience above-median OS exhibited a non-quasi-mesenchymal subtype (p < 0.001). ML application to ADC radiomics allowed OS prediction with a high diagnostic accuracy in an IVC. The high overlap of clinically relevant histopathological subtypes with model predictions underlines the potential of quantitative imaging in PDAC pre-operative subtyping and prognosis.

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A machine learning model for the prediction of survival and tumor subtype in pancreatic ductal adenocarcinoma from preoperative diffusion-weighted imaging

BACKGROUND This study aimed to compare superb microvascular imaging (SMI) with grayscale ultrasound (US) and color Doppler flow imaging (CDFI) to evaluate vascular distribution and morphology to distinguish between benign and malignant thyroid nodules. MATERIAL AND METHODS Seventy-one patients with 76 thyroid nodules underwent grayscale US, CDFI, and SMI thyroid imaging. CDFI and SMI assessed vascular quantity, morphology, and distribution, and was graded according to Adler's method, as absent (grade 0), minimal (grade 1), moderate (grade 2), or marked (grade 3). The detection of malignancy was compared between the following imaging groups, grayscale US alone, US combined with CDFI, and US combined with SMI. RESULTS SMI was significantly more accurate in identifying malignant thyroid nodules (79.3%) compared with CDFI (55.2%) (P<0.001). In malignant thyroid nodules, penetrating blood vessels were identified by SMI in 62.1% and by CDFI in 41.4%; there was no significant difference in vascular distribution between SMI (P=0.835) and CDFI (P=0.806). Grayscale US with SMI resulted in the greatest diagnostic sensitivity, accuracy, and specificity (86.21%, 85.53%, and 85.11%) compared with grayscale US with CDFI (75.86%, 82.89%, and 87.23%). Receiver operating characteristic (ROC) area under the curve (AUC) values of US with SMI, US with CDFI, and US alone were 0.918 (95% CI, 0.856-0.979), 0.911 (95% CI, 0.849-0.973), and 0.847 (95% CI, 0.762-0.932), respectively (P<0.001). CONCLUSIONS SMI as an adjunct to grayscale US provided significantly more information on vascularity associated with malignancy in thyroid nodules, when compared with grayscale US or with US and CDFI.

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A Prospective Study to Compare Superb Microvascular Imaging with Grayscale Ultrasound and Color Doppler Flow Imaging of Vascular Distribution and Morphology in Thyroid Nodules.

Ultrasound often represents the first diagnostic step for thyroid nodule evaluation in clinical practice, but baseline US alone is not always effective enough to achieve thyroid nodule characterization. In the last decades new ultrasound techniques, such as CEUS, have been introduced to evaluate thyroid parenchyma as recommended by EFSUMB guidelines, for use in clinical research field, although its role is not yet clear. Several papers show the potential utility of CEUS in the differential diagnosis of benign and malignant thyroid nodules and in the analysis of lymph node involvement in neoplastic pathology. Therefore, we carried out an evaluation of the literature concerning the role of CEUS in three specific areas: the characterization of the thyroid nodule, the evaluation of minimally invasive treatment and loco-regional staging of the lymph node in proven thyroid cancer. According to evidence reported, CEUS can also play an operative role in nodular thyroid pathology as it is able to guide ablation procedures on thyroid nodule and metastatic lymph nodes, to assess the radicality of surgery, to evaluate disease relapse at the level of the margins of ablated regions and to monitor the clinical evolution of necrotic areas in immediate post-treatment setting.

The Role of CEUS in the Evaluation of Thyroid Cancer: From Diagnosis to Local Staging

The utility of superb microvascular imaging (SMI) for evaluating hand joint lesions in patients with rheumatoid arthritis (RA) in clinical remission is unreported. This study aimed to compare SMI and power Doppler imaging (PDI) for the evaluation of hand joint lesions in these patients. Twenty-six patients with RA in clinical remission were enrolled. A total of 572 joints (52 wrist, 260 proximal interphalangeal, and 260 metacarpophalangeal joints) were detected by SMI and PDI. A semi-quantitative scale of 0–3 was used to compare the detection of synovial blood flow signal by SMI and PDI. Inter-observer agreement for the assessment of SMI and PDI scores was measured with kappa values. In the ten healthy volunteers, SMI and PDI signals were both scored 0. In the 26 RA patients, the remission rate via PDI was 65.4% but was only 42.3% via SMI. SMI also detected microvessel flow signal in seven patients diagnosed with clinical remission via PDI. Moreover, a total of 106 blood flow signals (18.5%) were detected by SMI, while 50 blood flow signals (8.7%) were detected by PDI. Compared with PDI, SMI increased 18.0% of power flow signals from Grade 0–1 and increased 13.7% of power flow signals from Grade 1–2. One joint classified as Grade 1 by PDI was classified as Grade 0 by SMI. Inter-observer agreement for PDI and SMI semi-quantitative scoring was moderate (kappa = 0.463). SMI seems more sensitive than PDI for detecting hand joint lesions in RA in clinical remission PDI, and could aid the achievement of true remission in RA patients.

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Superb microvascular imaging (SMI) for evaluating hand joint lesions in patients with rheumatoid arthritis in clinical remission

Superb microvascular imaging (SMI) for depiction of microvascular flow in thyroid nodules was compared with color/power Doppler imaging (CDI/PDI) and contrast-enhanced ultrasonography (CEUS). In addition, the diagnostic performance of conventional ultrasound combined with SMI for differentiating benign and malignant thyroid nodules was evaluated. Preoperative conventional ultrasound consisting of gray-scale ultrasonography and CDI/PDI, followed by SMI and CEUS, was used to record 52 thyroid nodules. Two radiologists analyzed the gray-scale ultrasound signs and nodules’ microvascular flow patterns to differentiate between benign (n = 13) and malignant nodules (n = 39). SMI was significantly more effective in the detection of microvascular flow signals than CDI/PDI. In malignant nodules, SMI depicted the presence of incomplete surrounding periphery microvasculature and of disordered heterogeneous internal microvasculature. Benign nodules showed complete surrounding periphery microvasculature (ring sign) and homogeneity internal branching. The accuracies of conventional ultrasound combined with CDI/ PDI, SMI, or CEUS for predicting malignancy were 67.31, 86.54, and 92.31%, respectively. The accuracy of SMI differed significantly from CDI/PDI (P = 0.012), but not from CEUS (P = 0.339). Microvascular flow and vessel branching in the peripheral and internal microvasculature of thyroid nodules is depicted with greater detail and clarity with SMI compared with conventional ultrasound. SMI offers a safe and low-cost alternative to CEUS for differentiating between benign and malignant thyroid nodules.

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Superb microvascular imaging (SMI) compared with conventional ultrasound for evaluating thyroid nodules.

Primary hyperparathyroidism (PHPT) results from an excess of parathyroid hormone (PTH) produced from an overactive parathyroid gland. The study aimed to explore the sonographic features of parathyroid adenomas and assess the diagnostic performance of ultrasonography (US) and Tc-99m MIBI SPECT/CT for preoperative localization of parathyroid adenomas. A total of 107 patients were enrolled in this retrospective study who had PHPT and underwent parathyroidectomy. Of the 107 patients, 97 performed US and Tc-99m MIBI SPECT/CT examinations for preoperative localization of parathyroid nodules. The sensitivity and accuracy of each modality were calculated. In this study, residual parathyroid sign and polar vascular sign were identified as characteristic US features of parathyroid adenomas. These manifestations were closely related to the size of the abnormal parathyroid lesions. Among the 108 parathyroid nodules from 97 patients with PHPT, the sensitivity and accuracy of US for locating the parathyroid nodules were significantly higher than those of Tc-99m MIBI SPECT/CT (93.0% vs. 63.0% and 88.0% vs. 63.0% respectively; χ2 = 26.224, 18.227 respectively, P < 0.001). The differences between US + Tc-99m MIBI SPECT/CT and Tc-99m MIBI SPECT/CT-alone were statistically significant (χ2 = 33.410, 21.587 respectively, P < 0.001), yet there were no significant differences in the sensitivity or accuracy between US + Tc-99m MIBI SPECT/CT and US-alone (χ2 = 0.866, 0.187 respectively, P = 0.352 and 0.665). US shows significantly better sensitivity and accuracy for localization of parathyroid adenomas than Tc-99m MIBI SPECT/CT. However, US combined with Tc-99m MIBI SPECT/CT is of great clinical value in the preoperative localization of parathyroid nodules in patients with PHPT.

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Efficacy of ultrasonography and Tc-99m MIBI SPECT/CT in preoperative localization of parathyroid adenomas causing primary hyperthyroidism

PURPOSE To explore the application value of SMI scoring assignment method combined with 2017 American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS) in differentiating benign and malignant thyroid nodules. METHODS According to the 2017 ACR TI-RADS classification, the enrolled nodules were divided into 3 points group, 4 points group, 5 points group, 6 points group and≥7 points group. The nodules were assigned scores according to the echocity of the nodules and the microvessels detected by SMI and their distribution patterns based on ACR TI-RADS. Accompany with the scores increased or decreased after assignment, the thyroid nodules were re-grouped. RESULTS The AUC after the scores assignment is better than before (Z = 3.881, P < 0.001). The specificity, positive predictive value and accuracy after score assigned are better than those of before (Z = 8.323, P < 0.001; Z = 8.619, P < 0.001; Z = 5.345, P < 0.001), there is no statistical difference in sensitivity before and after score assigned (Z = -0.513, P = 0.60), and the negative predictive value before assigned score is better than that of after (Z = -3.826, P < 0.001). CONCLUSION The diagnostic efficacy after scoring was better than that of before.

The value of superb microvascular imaging (SMI) scoring assignment method in differentiating benign and malignant thyroid nodules by conventional ultrasound.

Aim Intrathyroidal parathyroid adenoma (IPA) is rare and may easily be mistaken for thyroid nodule in ultrasonography. The aim of this study was to investigate the characteristic features of IPA and explore the value of preoperative and intraoperative ultrasound in the diagnosis and localization of IPA. Methods 13 of 216 patients who were found to have intrathyroidal parathyroid lesions underwent parathyroidectomy in our hospital because of PHPT. According to the relationship between parathyroid adenoma and thyroid gland, parathyroid adenoma was divided into extra-thyroid type or intra-thyroid type (partial or complete) and the results were compared with surgical and histopathological reports as gold standard. The sonographic features of intrathyroidal parathyroid lesions were analyzed retrospectively. Results A total of 12 intrathyroidal lesions showed profoundly hypoechoic solid nodules with well-defined border, abundant blood flow and polar feeding vessels originating from the superior or inferior thyroid artery (92.3%, 12/13). These nodules were finally confirmed as IPA (or IPAC) after surgery. Polar feeding vessel was not detected in one case of parathyroid hyperplasia confirmed by pathology (7.7%, 1/13). 12 cases were diagnosed and localized on ultrasonography before operation and 10 cases were localized on Tc-99m MIBI SPECT/CT. Conclusions The color Doppler ultrasound findings of IPA were confirmed as profoundly hypoechoic nodules with clear boundary and abundant internal blood flow. The presence of polar feeding vessels which originate from thyroid artery were identified as characteristic features of US for IPA. Preoperative and intraoperative ultrasound could be helpful in the localization and treatment of intrathyroidal parathyroid diseases.

The Value of Preoperative and Intraoperative Ultrasound in the Localization of Intrathyroidal Parathyroid Adenomas.

Purpose Accurate preoperative localization of tumor-bearing lesions is crucial for the successful surgical management of suspected recurrent parathyroid carcinoma. The purpose of this study was to evaluate the diagnostic value of 99m-technetium-labeled methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) and cervical ultrasound, individually and in combination, for preoperative localization of recurrent/metastatic lesions. We also analyzed the value of 99mTc-MIBI SPECT/CT in detecting ectopic lesions in patients with suspected recurrent parathyroid carcinoma. Methods Twenty-nine patients with suspected recurrent parathyroid carcinoma were included in this retrospective cohort study. Patients underwent preoperative 99mTc-MIBI SPECT/CT and cervical ultrasound. The reference standard was postsurgical histopathology. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy of the two diagnostic modalities alone and in combination were analyzed. Results Of the 29 patients, histopathological results revealed 48 metastases/recurrent lesions in 26 patients. The diagnostic value of 99mTc-MIBI SPECT/CT, cervical ultrasound, and the two modalities in combination were compared for the 27 patients who underwent new cervical surgery. Patient-level analysis of the combined use of 99mTc-MIBI SPECT/CT and cervical ultrasound had the highest sensitivity (100.00%) and accuracy (96.30%). At the lesion level, 99mTc-MIBI SPECT/CT had the highest specificity and PPV, at 100.00% respectively, whereas the combined use of 99mTc-MIBI SPECT/CT and cervical ultrasound had the highest sensitivity, at 97.62%. Moreover, 99mTc-MIBI SPECT/CT detected six ectopic lesions, and five of them showed increased 99mTc-MIBI uptake. Conclusions The combined use of 99mTc-MIBI SPECT/CT and cervical ultrasound is the most efficient strategy in the diagnosis of parathyroid carcinoma relapse, whereas 99mTc-MIBI SPECT/CT is the preferred method for localizing and analyzing cervical and extra-cervical lesions before the new surgery.

Ruigang Lu

Papers

Superb microvascular imaging (SMI) compared with conventional ultrasound for evaluating thyroid nodules.

Efficacy of ultrasonography and Tc-99m MIBI SPECT/CT in preoperative localization of parathyroid adenomas causing primary hyperthyroidism

The value of superb microvascular imaging (SMI) scoring assignment method in differentiating benign and malignant thyroid nodules by conventional ultrasound.

The Value of Preoperative and Intraoperative Ultrasound in the Localization of Intrathyroidal Parathyroid Adenomas.

Value of 99mTc-MIBI SPECT/CT in the localization of recurrent lesions in patients with suspected recurrent parathyroid carcinoma