How to Perform Intra-Operative Contrast-Enhanced Ultrasound of the Brain-A WFUMB Position Paper.

Intra-operative ultrasound has become a relevant imaging modality in neurosurgical procedures. While B-mode, with its intrinsic limitations, is still considered the primary ultrasound modality, intra-operative contrast-enhanced ultrasound (ioCEUS) has more recently emerged as a powerful tool in neurosurgery. Though still not used on a large scale, ioCEUS has proven its utility in defining tumor boundaries, identifying lesion vascular supply and mapping neurovascular architecture. Here we propose a step-by-step procedure for performing ioCEUS analysis of the brain, highlighting its neurosurgical applications. Moreover, we provide practical advice on the use of ultrasound contrast agents and review technical ultrasound parameters influencing ioCEUS imaging.

COVID-19 pneumonia manifestations at the admission on chest ultrasound, radiographs, and CT: single-center study and comprehensive radiologic literature review.

PURPOSE: To investigate the imaging features of emerging COVID-19 pneumonia on chest ultrasound (US), radiographs (CXR) and computed tomography (CT) examinations performed at admission and to provide a comprehensive radiological literature review on ongoing radiological data from recent publications. MATERIALS AND METHODS: In this retrospective single-center study, we enrolled consecutive patients from February 15, 2020, to March 15, 2020, with laboratory-confirmed SARS-CoV-2 hospitalized in Valduce Hospital (Como, Italy). Multi-modality imaging findings were evaluated and compared. Literature research was conducted through a methodical search on Pubmed and Embase databases. RESULTS: Fifty-eight patients (36 men, 22 women; age range, 18-98 years) were included in the study. Among these, chest US, CXR, and CT were performed respectively in twenty-two, thirty-two and forty-two patients. Lung US findings were consistent with diffuse B lines (100%) and subpleural consolidations (27.3%). CXR showed prevalent manifestations of consolidations (46.9%) and hazy increased opacities (37.5%). Typical CT features included bilateral and multilobar ground-glass opacities (GGO) with (59.5%) and without (35.7%) consolidations having a predominantly peripheral distribution (64.3%). Other imaging features included crazy paving pattern (57.1%), fibrous stripes (50%), subpleural lines (35.7%), architectural distortion (28.6%), air bronchogram sign (26.2%), vascular thickening (23.8%) and nodules (2.4%). Also, enlarged lymph nodes (14.3 %) and pleural effusion (7.1%) were observed. The literature review identified twenty-six original studies supporting our imaging chest findings. CONCLUSION: The spectrum of chest imaging manifestations of COVID-19 pneumonia upon admission includes B-lines and consolidations on US, consolidations and hazy increased opacities on CXR, and multifocal GGO with consolidations on CT.

Haematemesis and acute dysphagia: oesophagogastroduodenoscopy or CT-which one first?

We present an uncommon case of a patient presenting at the emergency department for severe vomiting, persisting for at least 12 hours, without nausea or abdominal pain. She initially referred vomiting food eaten several hours earlier and eventually a single episode of haematemesis with emission of a small amount of red blood and clots. She also reported the occurrence of acute dysphagia for solid food. The patient underwent oesophagogastroduodenoscopy (OGD), which showed that the lumen was almost completely narrowed by a submucosal bluish bulging from midoesophagus (19 cm from the incisors) to the cardia (located at 35 cm from the incisors). She therefore underwent chest CT showing a 15 cm long intramural oesophageal haematoma. Although the combination of vomiting and haematemesis is usually associated with Mallory-Weiss syndrome, in which a prompt OGD has a key role in the patient management, when these symptoms are associated with acute dysphagia, a possible intramural haematoma might be suspected. In this case, chest CT should take precedence, because it allows a quick and complete diagnostic appraisal. However, in this setting, although OGD can directly show typical findings (bluish swelling mucosa with or without a superficial tears), it might increase the risk of oesophageal haematoma rupture and intraluminal bleeding.

Identification of residual tumor with intraoperative contrast-enhanced ultrasound during glioblastoma resection.

OBJECTIVE: The purpose of this study was to assess the capability of contrast-enhanced ultrasound (CEUS) to identify residual tumor mass during glioblastoma multiforme (GBM) surgery, to increase the extent of resection. METHODS: The authors prospectively evaluated 10 patients who underwent surgery for GBM removal with navigated ultrasound guidance. Navigated B-mode and CEUS were performed prior to resection, during resection, and after complete tumor resection. Areas suspected for residual tumors on B-mode and CEUS studies were localized within the surgical field with navigated ultrasound and samples were sent separately for histopathological analysis to confirm tumor presence. RESULTS: In all cases tumor remnants were visualized as hyperechoic areas on B-mode, highlighted as CEUS-positive areas, and confirmed as tumoral areas on histopathological analysis. In 1 case only, CEUS partially failed to demonstrate residual tumor because the residual hyperechoic area was devascularized prior to ultrasound contrast agent injection. In all cases CEUS enhanced B-mode findings. CONCLUSIONS: As has already been shown in other neoplastic lesions in other organs, CEUS is extremely specific in the identification of residual tumor. The ability of CEUS to distinguish between tumor and artifacts or normal brain on B-mode is based on its capacity to show the vascularization degree and not the echogenicity of the tissues. Therefore, CEUS can play a decisive role in the process of maximizing GBM resection.

EVAR: Benefits of CEUS for monitoring stent-graft status.

Endo vascular aortic repair [EVAR] is performed with low peri-operative morbidity and mortality rate and short hospital stay. However, EVAR needs a close and lifelong imagining surveillance for a timely detection of possible complications including endoleaks, graft migration, fractures, and enlargement of aneurysm sac size with eventual rupture. Contrast enhanced computed tomography [CTA] is actually considered the gold-standard in EVAR follow-up, but it is accompanied with radiation burden and renal injury due to the use of contrast media. In the last two decades several studies have shown the role of contrast enhanced ultrasound [CEUS] in post-EVAR surveillance, with very good diagnostic performance, absence of renal impairment, and no radiation, accompanied by low costs, in comparison with CTA. In numerous prospective studies and meta-analyses the detection and characterization of endoleaks with CEUS is comparable to that of CTA imaging. Nowadays, in the EVAR surveillance novel strategies which involve CEUS with a central role, are suggested by several authors and applied in many institutions. In this review article we will present a comprehensive overview and analyses of the literature on the CEUS state-of-art imagining of EVAR follow-up, with its technique, findings, diagnostic accuracy, and its role in the follow up program.

Intraoperative Navigated Angiosonography for Skull Base Tumor Surgery.

BACKGROUND: One of the main challenges during skull base tumor surgery is identifying the relationships between the lesion and the principal intracranial vessels. To this end, neuronavigation systems based on preoperative imaging lack accuracy because of brain shift and brain deformation. Intraoperative navigated B-mode ultrasonography is useful in defining the extent of brain tumor. Doppler imaging adds information regarding flow entity in neighboring vessels. Second-generation ultrasound contrast agents improve the signal-to-noise ratio of B-mode imaging and permit the study of the vessel's course, blood flow, and perfusion characteristics of focal lesions. We report our experience using intraoperative navigated contrast-enhanced ultrasound to perform a navigated angiosonography (N-ASG) for the visualization of vessels in a series of 18 skull base tumors. METHODS: We performed N-ASG in a series of 18 skull base tumors (10 meningiomas, 3 craniopharyngiomas, 2 giant pituitary adenomas, 1 posterior fossa epidermoid, 2 dermoid cysts). N-ASG was obtained after craniotomy before resecting each lesion and during tumor removal, after intravenous injection of ultrasound contrast agent. RESULTS: In all 18 cases, major vessels and their branches were simultaneously identified (both high and low flow) using N-ASG, which allowed to visualize the whole length of each vessels. N-ASG was also useful in highlighting the lesion, compared with standard B-mode imaging, and showing its perfusion patterns. CONCLUSIONS: N-ASG can be applied to skull base tumor surgery, providing helpful information about the relationship between principal intracranial vessels and tumors. This technique could be of assistance in approaching the tumor and avoiding vascular damages.

Intraoperative cerebral glioma characterization with contrast enhanced ultrasound.

BACKGROUND: Contrast enhanced ultrasound (CEUS) is a dynamic and continuous modality providing real-time view of vascularization and flow distribution patterns of different organs and tumors. Nevertheless its intraoperative use for brain tumors visualization has been performed few times, and a thorough characterization of cerebral glioma had never been performed before. AIM: To perform the first characterization of cerebral glioma using CEUS and to possibly achieve an intraoperative differentiation of different gliomas. METHODS: We performed CEUS in an off-label setting in 69 patients undergoing surgery for cerebral glioma. An intraoperative qualitative analysis was performed comparing iCEUS with B-mode imaging. A postprocedural semiquantitative analysis was then performed for each case, according to EFSUMB criteria. Results were related to histopathology. RESULTS: We observed different CE patterns: LGG show a mild, dotted CE with diffuse appearance and slower, delayed arterial and venous phase. HGG have a high CE with a more nodular, nonhomogeneous appearance and fast perfusion patterns. CONCLUSION: Our study characterizes for the first time human brain glioma with CEUS, providing further insight regarding these tumors' biology. CEUS is a fast, safe, dynamic, real-time, and economic tool that might be helpful during surgery in differentiating malignant and benign gliomas and refining surgical strategy.

Intraoperative contrast-enhanced ultrasound for brain tumor surgery.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a dynamic and continuous modality that offers a real-time, direct view of vascularization patterns and tissue resistance for many organs. Thanks to newer ultrasound contrast agents, CEUS has become a well-established, live-imaging technique in many contexts, but it has never been used extensively for brain imaging. The use of intraoperative CEUS (iCEUS) imaging in neurosurgery is limited. OBJECTIVE: To provide the first dynamic and continuous iCEUS evaluation of a variety of brain lesions. METHODS: We evaluated 71 patients undergoing iCEUS imaging in an off-label setting while being operated on for different brain lesions; iCEUS imaging was obtained before resecting each lesion, after intravenous injection of ultrasound contrast agent. A semiquantitative, offline interobserver analysis was performed to visualize each brain lesion and to characterize its perfusion features, correlated with histopathology. RESULTS: In all cases, the brain lesion was visualized intraoperatively with iCEUS. The afferent and efferent blood vessels were identified, allowing evaluation of the time and features of the arterial and venous phases and facilitating the surgical strategy. iCEUS also proved to be useful in highlighting the lesion compared with standard B-mode imaging and showing its perfusion patterns. No adverse effects were observed. CONCLUSION: Our study is the first large-scale implementation of iCEUS in neurosurgery as a dynamic and continuous real-time imaging tool for brain surgery and provides the first iCEUS characterization of different brain neoplasms. The ability of CEUS to highlight and characterize brain tumor will possibly provide the neurosurgeon with important information anytime during a surgical procedure.

Accuracy of capsule colonoscopy and computed tomographic colonography in individuals with positive results from the fecal occult blood test.

BACKGROUND & AIMS: Computed tomographic colonography (CTC) is a reliable option for screening subjects who are unable or unwilling to undergo optical colonoscopy (OC). A colon capsule (PillCam Colon2 [CC2]; GivenImaging Ltd., Yokneam, Israel) has shown promising results in detecting polyps larger than 6 mm. We compared the accuracy of CC2 and CTC in identifying individuals with at least 1 polyp greater than 6 mm and subjects' attitude toward the procedures. METHODS: Fifty individuals (mean age, 59.2 ± 5.8 y; 58% male) with positive results from the immunochemical fecal occult blood test (iFOBT-positive) underwent CC2, CTC, and OC. The unblinded colonoscopy, integrating OC, CTC, and CC2 results, was used as the reference standard. In a per-patient analysis, the accuracy of CC2 and CTC were assessed for individuals with at least 1 polyp 6 mm or larger. Individuals were asked to choose which procedure they would be willing to repeat between CTC and CC2. RESULTS: The combination of OC, CTC, and CC2 identified 16 cases with at least 1 polyp 6 mm or larger (reference standard). CTC identified the polyps with 88.2% sensitivity, 84.8% specificity, a 3.0 positive likelihood ratio, and a 0.07 negative likelihood ratio. CC2 identified the polyps with 88.2% sensitivity, 87.8% specificity, a 3.75 positive likelihood ratio, and a 0.06 negative likelihood ratio. Thirty-nine subjects (78%) said they preferred CC2 to CTC. CONCLUSIONS: CC2 and CTC detect polyps 6 mm and larger with high levels of accuracy; these techniques are effective in selecting iFOBT-positive individuals who do not need to be referred for colonoscopy. CC2 seems to be better tolerated than CTC, and could be a reliable alternative to CTC for iFOBT-positive individuals who are unable or unwilling to undergo OC. ClinicalTrials.gov number: NCT01744509.

Re-thinking the role of motor cortex: context-sensitive motor outputs?

The standard account of motor control considers descending outputs from primary motor cortex (M1) as motor commands and efference copy. This account has been challenged recently by an alternative formulation in terms of active inference: M1 is considered as part of a sensorimotor hierarchy providing top-down proprioceptive predictions. The key difference between these accounts is that predictions are sensitive to the current proprioceptive context, whereas efference copy is not. Using functional electric stimulation to experimentally manipulate proprioception during voluntary movement in healthy human subjects, we assessed the evidence for context sensitive output from M1. Dynamic causal modeling of functional magnetic resonance imaging responses showed that FES altered proprioception increased the influence of M1 on primary somatosensory cortex (S1). These results disambiguate competing accounts of motor control, provide some insight into the synaptic mechanisms of sensory attenuation and may speak to potential mechanisms of action of FES in promoting motor learning in neurorehabilitation.

Detection of hepatocellular carcinoma and liver metastases with BR14: a multicenter phase IIA study.

The study was designed primarily to find the optimal dosage range of BR14 contrast-enhanced ultrasonography (CEUS) to detect malignant focal liver lesions. Secondary objectives were the evaluation of the safety profile and comparison with contrast-enhanced MRI (CE MRI). We studied 25 patients (9 females, 16 males, mean age, 66 years) with known hepatocellular carcinoma or liver metastases at 3 centers over a 3-month period. Each patient underwent a baseline examination and at least 3 CEUS examinations with ascending dose levels (0.25 mL; 1.0 mL; 4.0 mL) of BR14. CE MRI was performed 4 weeks before or after the CEUS examination. Dedicated liver maps were used to record the location, size, and type of detected lesions. Examination quality was documented and safety parameters were assessed. The number of lesions detected by BR14 CEUS increased with dosage, whereas the number of missed lesions and the lesion sizes decreased. Despite the increasing contrast enhancement, substantial differences among dosages were not seen for other image quality parameters. No significant changes were noted in safety parameters and no serious adverse events were reported. We conclude that the recommended dose level of BR14 is between 1 mL and 4 mL; at this dosage, lesion detection is comparable to that of CE MRI.

fMRI brain mapping during motion capture and FES induced motor tasks: signal to noise ratio assessment.

Functional Electrical Stimulation (FES) is a well known clinical rehabilitation procedure, however the neural mechanisms that underlie this treatment at Central Nervous System (CNS) level are still not completely understood. Functional magnetic resonance imaging (fMRI) is a suitable tool to investigate effects of rehabilitative treatments on brain plasticity. Moreover, monitoring the effective executed movement is needed to correctly interpret activation maps, most of all in neurological patients where required motor tasks could be only partially accomplished. The proposed experimental set-up includes a 1.5 T fMRI scanner, a motion capture system to acquire kinematic data, and an electro-stimulation device. The introduction of metallic devices and of stimulation current in the MRI room could affect fMRI acquisitions so as to prevent a reliable activation maps analysis. What we are interested in is that the Blood Oxygenation Level Dependent (BOLD) signal, marker of neural activity, could be detected within a given experimental condition and set-up. In this paper we assess temporal Signal to Noise Ratio (SNR) as image quality index. BOLD signal change is about 1-2% as revealed by a 1.5 T scanner. This work demonstrates that, with this innovative set-up, in the main cortical sensorimotor regions 1% BOLD signal change can be detected at least in the 93% of the sub-volumes, and almost 100% of the sub-volumes are suitable for 2% signal change detection. The integrated experimental set-up will therefore allows to detect FES induced movements fMRI maps simultaneously with kinematic acquisitions so as to investigate FES-based rehabilitation treatments contribution at CNS level.

Simultaneous measurements of kinematics and fMRI: compatibility assessment and case report on recovery evaluation of one stroke patient.

BACKGROUND: Correlating the features of the actual executed movement with the associated cortical activations can enhance the reliability of the functional Magnetic Resonance Imaging (fMRI) data interpretation. This is crucial for longitudinal evaluation of motor recovery in neurological patients and for investigating detailed mutual interactions between activation maps and movement parameters.Therefore, we have explored a new set-up combining fMRI with an optoelectronic motion capture system, which provides a multi-parameter quantification of the performed motor task. METHODS: The cameras of the motion system were mounted inside the MR room and passive markers were placed on the subject skin, without any risk or encumbrance. The versatile set-up allows 3-dimensional multi-segment acquisitions including recording of possible mirror movements, and it guarantees a high inter-sessions repeatability.We demonstrated the integrated set-up reliability through compatibility tests. Then, an fMRI block-design protocol combined with kinematic recordings was tested on a healthy volunteer performing finger tapping and ankle dorsal- plantar-flexion. A preliminary assessment of clinical applicability and perspectives was carried out by pre- and post rehabilitation acquisitions on a hemiparetic patient performing ankle dorsal- plantar-flexion. For all sessions, the proposed method integrating kinematic data into the model design was compared with the standard analysis. RESULTS: Phantom acquisitions demonstrated the not-compromised image quality. Healthy subject sessions showed the protocols feasibility and the model reliability with the kinematic regressor. The patient results showed that brain activation maps were more consistent when the images analysis included in the regression model, besides the stimuli, the kinematic regressor quantifying the actual executed movement (movement timing and amplitude), proving a significant model improvement. Moreover, concerning motor recovery evaluation, after one rehabilitation month, a greater cortical area was activated during exercise, in contrast to the usual focalization associated with functional recovery. Indeed, the availability of kinematics data allows to correlate this wider area with a higher frequency and a larger amplitude of movement. CONCLUSIONS: The kinematic acquisitions resulted to be reliable and versatile to enrich the fMRI images information and therefore the evaluation of motor recovery in neurological patients where large differences between required and performed motion can be expected.

CEUS in abdominal trauma: multi-center study.

The objective of this study was to evaluate the concordance of US and contrast-enhanced US (CEUS) with CT in the assessment of solid organ injury following blunt trauma. Patients underwent complete US examination, including free fluid search and solid organ analysis. CEUS followed, using low-mechanical index techniques and SonoVue. CT was performed within 1 h. Among 156 enrolled patients, 91 had one or more abnormalities (n = 107) at CT: 26 renal, 38 liver, 43 spleen. Sensitivity, specificity, and accuracy for renal trauma at baseline US were 36%, 98%, and 88%, respectively, after CEUS values increased to 69%, 99%, and 94%. For liver baseline US values were 68%, 97%, and 90%; after CEUS were 84%, 99%, and 96%. For spleen, results were 77%, 96%, and 91% at baseline US and 93%, 99%, and 97% after CEUS. Per patient evaluation gave the following results in terms of sensitivity, specificity and accuracy: 79%, 82%, 80% at baseline US; 94%, 89%, and 92% following CEUS. CEUS is more sensitive than US in the detection of solid organ injury, potentially reducing the need for further imaging. False negatives from CEUS are due to minor injuries, without relevant consequences for patient management and prognosis.

Value of contrast-enhanced ultrasonography for detecting renal infarcts proven by contrast enhanced CT. A feasibility study.

The effectiveness of contrast-enhanced ultrasonography (CEUS) in the evaluation of patients with acute renal infarcts was investigated, using contrast-enhanced helical computed tomography (CT) as the reference imaging procedure. Twenty-seven consecutive patients with acute renal infarcts detected with contrast-enhanced helical CT underwent CEUS. Digital cine-clips of CEUS were evaluated by two independent readers blinded to CT findings. Image quality was rated subjectively on a four-point scale. Then, readers were asked to assign a confidence level in diagnosis of renal infarct at the upper pole, medium portion, and lower pole of each kidney according to a five-degree scale, ranging from definitely absent to definitely present. ROC curve analysis was employed to assess the overall confidence of diagnosis of infarct, and weighted kappa values were calculated to assess inter-reader agreement. The subjective image quality of CEUS was lower than the image quality of CT at the upper poles. However, the diagnostic performance of CEUS was excellent (area under receiver-operator characteristic curve 0.992 +/- 0.006 for reader 1; 0.991 +/- 0.007 for reader 2), with very good inter-reader agreement (weighted kappa value = 0.83). CEUS is a reproducible tool to detect acute renal infarcts in men, with a diagnostic performance approaching that of CT.

Economic assessment of contrast-enhanced ultrasonography for evaluation of focal liver lesions: a multicentre Italian experience.

BACKGROUND: The aim of this study was to evaluate the clinical and economic consequences of the introduction of contrast-enhanced ultrasonography (CEUS) into the diagnostic clinical algorithm for the characterization of incidental focal liver lesions (FLLs). METHODS: This prospective study enrolled 485 subjects at three hospitals in Italy. Two diagnostic algorithms were utilized: (1) a classic patient work-up, which included baseline US followed by a CT or MR examination, and (2) a new patient management scheme in which, following the baseline US, a CEUS examination was performed. For each pathway, both direct and indirect health costs for the National Health System (NHS) at two of the three hospitals involved in the study were calculated. Clinical outcome was measured in terms of number of cases correctly diagnosed, using contrast-enhanced CT/contrast-enhanced MR as the reference standard. RESULTS: CEUS correctly differentiated (benign vs. malignant) 559 of 575 lesions (97.2%), with a sensitivity of 98.1% and a specificity of 95.7%. Histological characterization was correct in 502 of 575 lesions (87%) with a sensitivity of 90.5% and a specificity of 85.4%. In terms of cost, the conventional diagnostic algorithm incurred for the NHS a total cost of Euro 134.576,60 vs. Euro 55.674,30 with CEUS, for a saving of Euro 78.902 (Euro 162 per patient). For the hospitals, the total cost was Euro 147.045 without CEUS vs Euro 61.979 with CEUS, for a saving of Euro 85.065,96 or Euro 175,39 per patient. CONCLUSION: The routine use of CEUS for the characterization of FLLs provides significant cost savings, both for the NHS and for the hospital.

Elastosonography in the diagnosis of the nodular breast lesions: preliminary report.

PURPOSE: To assess the diagnostic accuracy of elastography in characterising nodular breast lesions. MATERIALS AND METHODS: A total of 82 patients who received mammographic, ultrasonographic and elastographic evaluation in a single session at two Italian centres (Dept of Radiology, Az. Ospedali Riuniti, Ancona, and Ospedale Valduce, Como, Italy) between January and August 2004 according to identical protocols exhibited 91 nodules that were subjected to cytological/histological examination. Lesions were classified and scored and the sensitivity and specificity of elastography calculated. RESULTS: Overall sensitivity and specificity were 79% and 89%, respectively. However, sensitivity was 86% and 65% and specificity 100% and 62% for lesions < 2 cm and > 2 cm in diameter, respectively. Despite the small sample and the fact that it does not include the full range of cell types, tumour cell composition seemed to affect accuracy. CONCLUSIONS: Elastography is easy and rapid to perform. Larger studies are needed to establish semiological patterns; despite the small patient sample, these data provide an interesting contribution.

[Current state of the use of sonographic contrast agents with low acoustic pressure techniques in the study of focal liver lesions].

Ultrasonography is the most commonly used screening modality for focal liver lesions in Europe. Over the past few years, to overcome the inherent limitations of B-mode imaging and colour-Doppler ultrasound in identifying and characterising focal liver lesions, intravenous agents capable of enhancing the ultrasound signal emitted by vascular and parenchymal structures have been developed. From December 1999 to December 2001, about 400 patients with a known tumour, HCV-related chronic cirrhotic liver disease, or with an indeterminate focal liver lesion discovered incidentally were evaluated by ultrasound of the liver parenchyma both in baseline conditions and after administration of contrast material. The ultrasound contrast agents used were: SonoVue (Bracco, Milan-Italy) and Optison (Mallinckrodt, London - UK). Our experience is based on low mechanical-index contrast-enhanced imaging, which acts conservatively, performed with different commercially available algorithms, in grey-scale mode alone (B-mode). We report the morphological patterns displayed by the main benign and malignant liver lesions after the administration of second-generation ultrasound contrast material, and review the main imaging patterns able to provide effective and practical guidance in formulating a diagnosis of benignity or malignancy. Our clinical experience confirmed the literature findings that the introduction of low mechanical index methods in grey-scale imaging has allowed qualitatively better results for detecting and characterising focal liver lesions than those obtained with baseline and colour-Doppler imaging. The ease of use, substantial repeatability and predictability of the enhancement effects obtainable with low mechanical index methods are the main reasons for the success of this approach. Broadening the scope of studies to obtain controlled data and comparisons with the other imaging modalities is crucial for the definitive validation of the method.