Freehand SPECT for image-guided sentinel lymph node biopsy in breast cancer.

PURPOSE: Sentinel lymph node biopsy (SLNB) is standard of care in early-stage breast cancer. Freehand SPECT (FhSPECT) is a system generating 3-D images for intraoperative visual detection of radioactivity in the body. The aim of our study was to evaluate the sensitivity of this technology for sentinel lymph node (SLN) detection and SLNB guidance. METHODS: In 40 patients, FhSPECT was additionally used after planar imaging and probe localization for SLNB. The number of SLNs detected was compared with the number detected by planar scintigraphy (reference method) and the conventional acoustic gamma probe (standard alternative). The sensitivity of FhSPECT was compared with that of the conventional gamma probe (McNemar's test). RESULTS: FhSPECT mapped the SLNs in 92.3 % of the basins (36/39) intraoperatively in identical positions to those seen on planar scintigrams. The conventional gamma probe correctly detected the SLNs in 35 of 39 basins (89.7 %). After SLNB, remaining radioactivity was detected by FhSPECT in nine patients, resulting in additional resection of SLNs in four patients. CONCLUSION: FhSPECT is a highly sensitive modality for intraoperative detection of SLNs, resulting in the identification of a higher number of SLNs than conventional gamma probe detection.

1D-3D registration for intra-operative nuclear imaging in radio-guided surgery.

3D functional nuclear imaging modalities like SPECT or PET provide valuable information, as small structures can be marked with radioactive tracers to be localized before surgery. This positional information is valuable during surgery as well, for example when locating potentially cancerous lymph nodes in the case of breast cancer. However, the volumetric information provided by pre-operative SPECT scans loses validity quickly due to posture changes and manipulation of the soft tissue during surgery. During the intervention, the surgeon has to rely on the acoustic feedback provided by handheld gamma-detectors in order to localize the marked structures. In this paper, we present a method that allows updating the pre-operative image with a very limited number of tracked readings. A previously acquired 3D functional volume serves as prior knowledge and a limited number of new 1D detector readings is used in order to update the prior knowledge. This update is performed by a 1D-3D registration algorithm that registers the volume to the detector readings. This enables the rapid update of the visual guidance provided to the surgeon during a radio-guided surgery without slowing down the surgical workflow. We evaluate the performance of this approach using Monte-Carlo simulations, phantom experiments and patient data, resulting in a positional error of less than 8 mm which is acceptable for surgery. The 1D-3D registration is also compared to a volumetric reconstruction using the tracked detector measurements without taking prior information into account, and achieves a comparable accuracy with significantly less measurements.

Prostate-specific membrane antigen-radioguided surgery for metastatic lymph nodes in prostate cancer.

With the advent of (68)Ga-labeled prostate-specific membrane antigen-N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid ((68)Ga-PSMA-HBED-CC) positron emission tomography (PET) hybrid imaging in prostate cancer (PCa), even small metastatic lymph nodes (LNs) can be visualized. However, intraoperative detection of such LNs may not be easy owing to their inconspicuous morphology and/or atypical localization. The aim of our feasibility study was to evaluate PSMA-radioguided surgery for detection of metastatic LNs. One patient with primary PCa and evidence of LN metastases and four PCa patients with evidence of recurrent disease to regional LNs on (68)Ga-PSMA-HBED-CC PET hybrid imaging received an intravenous injection of an (111)In-PSMA investigation and therapy agent 24h before surgery. Metastatic LNs were tracked intraoperatively using a gamma probe with acoustic and visual feedback. All radioactive-positive LN specimens detected in vivo were confirmed by ex vivo measurements and corresponded to PSMA-avid metastatic disease according to histopathology analysis. Intraoperative use of the gamma probe detected all PSMA-positive lesions identified on preoperative (68)Ga-PSMA-HBED-CC PET. Detection of small subcentimeter metastatic LNs was facilitated, and PSMA-radioguided surgery in two patients revealed additional lesions close to known tumor deposits that were not detected by preoperative (68)Ga-PSMA-HBED-CC PET. However, greater patient numbers and long-term follow-up data are needed to determine the future role of PSMA-radioguided surgery.

First experience with image-guided resection of paraganglioma.

A 32-year-old male patient showed 2 focal uptakes of I-MIBG next to the left renal vein in a diagnostic scan, corresponding to paragangliomas. An operation was indicated, and to guide resection during surgery we used the freehand SPECT system. In the operating room, using freehand SPECT, both lesions were found. The system was of additional value in planning the operative access to the region of interest and in determining the depth of 1 lesion for precise and more rapid extirpation. Furthermore, it confirmed no residues in the operating field after resection of the tumors.

Mini gamma cameras for intra-operative nuclear tomographic reconstruction.

Nuclear imaging modalities like PET or SPECT are in extensive use in medical diagnostics. In a move towards personalized therapy, we present a flexible nuclear tomographic imaging system to enable intra-operative SPECT-like 3D imaging. The system consists of a miniaturized gamma camera mounted on a robot arm for flexible positioning, while spatio-temporal localization is provided by an optical tracking system. To facilitate statistical tomographic reconstruction of the radiotracer distribution using a maximum likelihood approach, a precise model of the mini gamma camera is generated by measurements. The entire system is evaluated in a series of experiments using a hot spot phantom, with a focus on criteria relevant for the intra-operative workflow, namely the number of required imaging positions as well as the required imaging time. The results show that high quality reconstructed images of simple hot spot configurations with positional errors of less than one millimeter are possible within acquisition times as short as 15s.

FhSPECT-US guided needle biopsy of sentinel lymph nodes in the axilla: is it feasible?

Until now, core needle biopsy of the axillary sentinel lymph nodes in early stage breast cancer patients is not possible, due to the lack of a proper combination of functional and anatomical information. In this work we present the first fully 3D freehand SPECT--ultrasound fusion, combining the advantages of both modalities. By using spatial positioning either with optical or with electromagnetic tracking for the ultrasound probe, and a mini gamma camera as radiation detector for freehand SPECT reconstructions, we investigate the capability of the introduced multi-model imaging system, where we compare both 3D freehand SPECT and 3D ultrasound to ground truth for a realistic breast mimicking phantom and further analyze the effect of tissue deformation by ultrasound. Finally, we also show its application in a real clinical setting.

Towards personalized interventional SPECT-CT imaging.

The development of modern robotics and compact imaging detectors allows the transfer of diagnostic imaging modalities to the operating room, supporting surgeons to perform faster and safer procedures. An intervention that currently suffers from a lack of interventional imaging is radioembolization, a treatment for hepatic carcinoma. Currently, this procedure requires moving the patient from an angiography suite for preliminary catheterization and injection to a whole-body SPECT/CT for leakage detection, necessitating a second catheterization back in the angiography suite for the actual radioembolization. We propose an imaging setup that simplifies this procedure using a robotic approach to directly acquire an interventional SPECT/CT in the angiography suite. Using C-arm CT and a co-calibrated gamma camera mounted on a robotic arm, a personalized trajectory of the gamma camera is generated from the C-arm CT, enabling an interventional SPECT reconstruction that is inherently co-registered to the C-arm CT. In this work we demonstrate the feasibility of this personalized interventional SPECT/CT imaging approach in a liver phantom study.

Combination of intra-operative freehand SPECT imaging with MR images for guidance and navigation.

Nowadays for clinical applications such as sentinel lymph node biopsy in breast or prostate cancer, only pre-operative image data is used for navigation, i.e. CT, SPECT/CT or PET/CT. Freehand SPECT and freehand PET provide intra-operative functional imaging techniques that can be complemented with pre- and intra-operative MR imaging to allow for better planning, navigation and guidance. In this paper we propose a method to enable navigation based on pre- or intra-operatively acquired MR images. A fully MR compatible phantom and a dedicated MR compatible optical tracking target with MR markers is built for this study. PET/MR, SPECT/CT and freehand SPECT scans of the phantom are performed. Registration is done using point based registration of the known marker and target geometries and a ground truth is obtained from a SPECT/CT and an MR image that are directly registered. The RMS errors was 0.31 mm for the ground truth and 3.29 mm when using segmentation of the MR markers and their spatial relationship with the optical tracking spheres of the dedicated target. Thus, the freehand SPECT can be registered easily by this approach without the need of any additional CT scans and therefore without any additional radiation dose for the patient. This enables intra-operative fusion of the pre- or intra-operatively acquired MR data, which could provide valuable additional information for intra-operative applications such as guidance based on accurate anatomy or verifying exact tumor location in combination with detailed morphological patient data.

Showcase of Intraoperative 3D Imaging of the Sentinel Lymph Node in a Breast Cancer Patient using the New Freehand SPECT Technology.

After the development of a hand-held intraoperative device for 3D real-time imaging of radioactively labeled sentinel lymph nodes in the human body, we present our first experience with the newest version of the freehand single-photon emission computed tomography (SPECT) technology in the operating room. The freehand SPECT system combines a gamma probe and an optical infrared positioning system, and provides surgeons with 3D imaging including exact depth information of the radioactive target. This technology was used intraoperatively in a female breast cancer patient to localize the axillary sentinel lymph nodes. The data obtained with freehand SPECT correlate well with conventional lymphoscintigraphy and with data collected using a conventional hand-held probe. By offering fast real-time intraoperative imaging, the new freehand SPECT system might facilitate the detection and removal of the sentinel lymph node(s) in certain situations and can be used for documentation and quality assurance purposes.