Massimiliano Del Bene

Fusion imaging for intra-operative ultrasound-based navigation in neurosurgery

The major shortcoming of image-guided navigation systems is the use of presurgically acquired image data, which does not account for intra-operative changes such as brain shift, tissue deformation and tissue removal occurring during the surgical procedure. Intra-operative ultrasound (iUS) is becoming widely used in neurosurgery but they lack orientation and panoramic view. In this article, we describe our procedure for US-based real-time neuro-navigation during surgery. We used fusion imaging between preoperative magnetic resonance imaging (MRI) and iUS for brain lesion removal in 67 patients so far. Surgical planning is based on preoperative MRI only. iUS images obtained during surgery are fused with the preoperative MRI. Surgery is performed under intra-operative US control. Relying on US imaging, it is possible to recalibrate navigated MRI imaging, adjusting distortion due to brain shift and tissue resection, continuously updating the two modalities. Ultrasound imaging provides excellent visualization of targets, their margins and surrounding structures. The use of navigated MRI is helpful in better understanding cerebral ultrasound images, providing orientation and panoramic view. Intraoperative US-guided neuro-navigation adjustments are very accurate and helpful in the event of brain shift. The use of this integrated system allows for a true real-time feedback during surgery.SommarioIl principale difetto della neurochirurgia guidata da immagini è il basarsi su immagini acquisite prima dell’intervento, che per ovvie ragioni non possono tenere conto di fenomeni intra-operatori come il brain-shift, la deformazione dei tessuti e l’asportazione di tessuto patologico. L’ecografia intra-operatoria (iUS) sta acquisendo sempre maggior rilevanza in ambito neurochirurgico ma è limitata dalla difficoltosa interpretazione dell’orientamento delle immagini e dalla scarsa panoramicità. In questo articolo descriviamo la nostra tecnica di neuronavigazione real-time basata sull’ecografia intra-operatoria. Fino ad ora abbiamo impiegato la fusione d’immagini tra la risonanza magnetica (MRI) pre-operatoria e l’iUS in 67 pazienti affetti da neoplasie cerebrali. La pianificazione dell’intervento e l’approccio chirurgico è basata sulla (MRI) pre-operatoria mentre l’intervento è guidato dall’iUS. Basandosi sull’iUS è possibile correggere la calibrazione delle immagini (MRI) pre-operatorie correggendo il brain-shift, aggiornando continuamente le due modalità. L’ecografia intra-operatoria permette una eccellente identificazione dei target, dei margini e delle strutture circostanti. L’uso del navigatore basato su (MRI) pre-operatoria è utile nella comprensione delle immagini ecografiche soprattutto per quanto riguarda l’orientazione e la visione panoramica. Le correzione del sistema di neuronavigazione basate sull’iUS sono accurate e utili nel caso di fenomeni intra-operatori come il brain-shift, la deformazione dei tessuti e l’asportazione di tessuto patologico. La neuronavigazione baasata sulla fusione d’immagini tra iUS e (MRI) pre-operatoria permette un vero feeback in real-time durante la chirurgia.

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.

From Grey Scale B-Mode to Elastosonography: Multimodal Ultrasound Imaging in Meningioma Surgery—Pictorial Essay and Literature Review

The main goal in meningioma surgery is to achieve complete tumor removal, when possible, while improving or preserving patient neurological functions. Intraoperative imaging guidance is one fundamental tool for such achievement. In this regard, intra-operative ultrasound (ioUS) is a reliable solution to obtain real-time information during surgery and it has been applied in many different aspect of neurosurgery. In the last years, different ioUS modalities have been described: B-mode, Fusion Imaging with pre-operative acquired MRI, Doppler, contrast enhanced ultrasound (CEUS), and elastosonography. In this paper, we present our US based multimodal approach in meningioma surgery. We describe all the most relevant ioUS modalities and their intraoperative application to obtain precise and specific information regarding the lesion for a tailored approach in meningioma surgery. For each modality, we perform a review of the literature accompanied by a pictorial essay based on our routinely use of ioUS for meningioma resection.

Intraoperative cerebral angiosonography with ultrasound contrast agents: how I do it

AbstractBackgroundIntraoperative vessel visualization is highly desirable, especially when the target is related to or close to main vessels, such as in the skull base and vascular surgery. Contrast-enhanced ultrasound (CEUS) is an imaging technique that allows visualization of tissue perfusion and vascularization through the infusion of purely intravascular ultrasound contrast agents (UCA).MethodsAfter cerebral scanning with B-mode ultrasound (US) CEUS is performed, UCA are injected and insonated with low mechanical index US. A UCA-specific harmonic signal is transduced using a contrast-specific algorithm to obtain real-time angiosonography (ASG).ConclusionsReal-time intraoperative ASG is a rapid, reliable, repeatable method for vessel visualization and evaluation of tissue perfusion.Key points• ASG permits to assess vessel position, dimension, and relationships; it also allows a qualitative evaluation of flow entity and direction. • ASG shows vessels in depth without the need of their direct exposure, as for fluorescence-guided surgery. • ASG permits to study the entire vascular tree without the necessity to set gain or pulse repetition frequency as in Doppler imaging. • Vessels of interest can be visualized following their entire length across the surgical field, along the arterial, capillary, and venous districts. • ASG scan is repeatable multiple times throughout the operation, and each exam could be recorded as a clip to be visualized at a later stage. • In case of neoplastic lesion, ASG characterizes the perfusion pattern in three phases: arterial, venous, and parenchymal, permitting to visualize afferent and efferent vessels, facilitating the surgical strategy. • During tumor debulking, ASG shows the remaining distance to major vessels, providing information to avoid direct vessel damage. • In tumor and AVM surgery, ASG shows nidus or tumoral remnants that might be covered by healthy tissue, thus not visible on the surface. • In case of aneurysm surgery, post-clipping angiosonographic control confirms proper aneurysm exclusion and distal vessels flow.

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 vessels 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.

Discrete or diffuse intramedullary tumor? Contrast-enhanced intraoperative ultrasound in a case of intramedullary cervicothoracic hemangioblastomas mimicking a diffuse infiltrative glioma: Technical note and case report

Hemangioblastomas are benign, highly vascularized intramedullary lesions that may also extend into the intradural space. Surgery represents the standard therapy, with the goal of obtaining complete resection even at the risk of neurological morbidity. MRI is the gold standard for diagnosis and assessment of intramedullary tumors. Nevertheless, sometimes MRI may not accurately differentiate between different types of intramedullary tumors, in particular if they are associated with syringes or intra- and peritumoral cysts. This could subsequently affect surgical strategies. Intraoperative ultrasound (ioUS) has become in the last few years a very useful tool for use during neurosurgical procedures. Various ioUS modalities such as B-mode and Doppler have been applied during neurosurgical procedures. On the other hand, the use of contrast-enhanced ultrasound (CEUS) is not yet well defined and standardized in this field. We report a case of a young patient harboring a cervicothoracic intramedullary tumor, for which the preoperative neuroradiologi-cal diagnosis was in favor of a diffuse astrocytoma with nodular components whereas ioUS demonstrated 3 distinct intramedullary nodules. CEUS showed highly vascularized lesions, compatible with hemangioblastomas. These findings, particularly those obtained with CEUS, allowed better definition of the lesions for diagnosis, enhanced understanding of the physiopathological aspects, and permitted the localization of all 3 nodules, thus limiting spinal cord manipulation and allowing complete resection of the lesions, with an uneventful postoperative neurological course. To the best of our knowledge, this is the first report of the use of intraoperative CEUS in a case of intramedullary hemangioblastoma.

Contrast-enhanced MR Imaging versus Contrast-enhanced US: A comparison in glioblastoma surgery by using intraoperative fusion imaging

Purpose To compare contrast material enhancement of glioblastoma multiforme (GBM) with intraoperative contrast-enhanced ultrasonography (US) versus that with preoperative gadolinium-enhanced T1-weighted magnetic resonance (MR) imaging by using real-time fusion imaging. Materials and Methods Ten patients with GBM were retrospectively identified by using routinely collected, anonymized data. Navigated contrast-enhanced US was performed after intravenous administration of contrast material before tumor resection. All patients underwent tumor excision with navigated intraoperative US guidance with use of fusion imaging between real-time intraoperative US and preoperative MR imaging. With use of fusion imaging, glioblastoma contrast enhancement at contrast-enhanced US (regarding location, morphologic features, margins, dimensions, and pattern) was compared with that at gadolinium-enhanced T1-weighted MR imaging. Results Fusion imaging for virtual navigation enabled matching of real-time contrast-enhanced US scans to corresponding coplanar preoperative gadolinium-enhanced T1-weighted MR images in all cases, with a positional discrepancy of less than 2 mm. Contrast enhancement of gadolinium-enhanced T1-weighted MR imaging and contrast-enhanced US was superimposable in all cases with regard to location, margins, dimensions, and morphologic features. The qualitative analysis of contrast enhancement pattern demonstrated a similar distribution in contrast-enhanced US and gadolinium-enhanced T1-weighted MR imaging in nine patients: Seven lesions showed peripheral inhomogeneous ring enhancement, and two lesions showed a prevalent nodular pattern. In one patient, the contrast enhancement pattern differed between the two modalities: Contrast-enhanced US showed enhancement of the entire bulk of the tumor, whereas gadolinium-enhanced T1-weighted MR imaging demonstrated peripheral contrast enhancement. Conclusion Glioblastoma contrast enhancement with contrast-enhanced US is superimposable on that provided with preoperative gadolinium-enhanced T1-weighted MR imaging regarding location, margins, morphologic features, and dimensions, with a similar enhancement pattern in most cases. Thus, contrast-enhanced US is of potential use in the surgical management of GBM.

Spinal Dural Arteriovenous Fistula: Is There a Role for Intraoperative Contrast-Enhanced Ultrasound?

BACKGROUND Intraoperative imaging during surgical ligation of a spinal dural arteriovenous fistula (SDAVF) is usually based on fluorescence angiography, intraoperative Doppler ultrasound, and intraoperative digital subtraction angiography. We investigated the potential role of contrast-enhanced ultrasound (CEUS) during surgical management of SDAVF. The main features of SDAVF on CEUS before treatment are described as well as their modifications after surgical ligation. CASE DESCRIPTION CEUS was performed using harmonic imaging with a second-generation ultrasound contrast agent in a case of right D6 SDAVF. Initial CEUS scan demonstrated the location of the arterialized vein draining in the dilated perimedullary plexus and augmented enhancement of the spinal cord secondary to intramedullary capillary congestion and augmented flow. The postligation scan demonstrated interruption of the arterialized vein and restoration of normal blood flow in spinal cord and perimedullary plexus. CONCLUSIONS CEUS allowed real-time visualization before and after ligation of the site of the fistula and blood flow changes occurring in the spinal cord and perimedullary plexus. CEUS is a valuable tool in SDAVF surgery without the limitations of Doppler imaging and possibly can be integrated with other imaging modalities such as fluorescence angiography.

Tumor-initiating cell frequency is relevant for glioblastoma aggressiveness.

Glioblastoma (GBM) is maintained by a small subpopulation of tumor-initiating cells (TICs). The arduous assessment of TIC frequencies challenges the prognostic role of TICs in predicting the clinical outcome in GBM patients. We estimated the TIC frequency in human GBM injecting intracerebrally in mice dissociated cells without any passage in culture. All GBMs contained rare TICsand were tumorigenic in vivo but only 54% of them grew in vitro as neurospheres. We demonstrated that neurosphere formation in vitro did not foretell tumorigenic ability in vivo and frequencies calculated in vitro overestimated the TIC content. Our findings assert the pathological significance of GBM TICs. TIC number correlated positively with tumor incidence and inversely with survival of tumor-bearing mice. Stratification of GBM patients according to TIC content revealed that patients with low TIC frequency experienced a trend towards a longer progression free survival. The expression of either putative stem-cell markers or markers associated with different GBM molecular subtypes did not associate with either TIC content or neurosphere formation underlying the limitations of TIC identification based on the expression of some putative stem cell-markers.

Intraoperative cerebral ultrasound for third ventricle colloid cyst removal: case report

AbstractPurposeTo assess the usefulness of intraoperative Ultrasound (ioUS) and Echo-Color-Doppler (ECD) for the surgical removal of a specific deep-sited lesion.MethodsCase report of a woman underwent surgery of a third ventricle colloid cyst removal.ResultsThe ioUS technique depicted the deep intraventricular lesion and all the anatomical structures surrounding the lesion; helping us defining the best trajectory for the safest surgical removal.ConclusionIn our experience ioUS and ECD have demonstrated to be a reliable and useful intraoperative tool in neurosurgery, not only for superficial tumors but for deep intraventicular lesions as well.RiassuntoObiettiviLo scopo di questo articolo è quello di mostrare l’utilizzo dell’ecografia intra operatoria, in B-mode ed Eco-Color-Doppler, durante un intervento di asportazione di lesione situata profondamente nelle strutture endocraniche cerebrali.Materiali e MetodiDescrizione di un caso clinico di asportazione chirurgica di una cisti colloide del terzo ventricolo per via trans-ventricolare frontale destra.RisultatiL’imaging ecografico intraoperatorio ha permesso di evidenziare e riconoscere precisamente la lesione endoventricolare e tutte le strutture circostanti, seppur situate profondamente, permettendo in tal modo durante l’intervento di assicurare la definizione del miglior approccio chirurgico per una asportazione completa e anatomicamente sicura.ConclusioniIn base alla nostra esperienza la tecnica ecografica si è dimostrate affidabile e sicura, durante le procedure neurochirurgiche di asportazione lesionale, non solo per le patologie superficiali (corticali/sottocorticali), ma anche nei casi di lesioni profonde e nel riconoscimento di strutture vitali.