Magnetic procedure for sentinel lymph node detection and evaluation of metastases: Design and rationale of the Lowmag trial

doi:10.21203/rs.3.rs-3750227/v1

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Magnetic procedure for sentinel lymph node detection and evaluation of metastases: Design and rationale of the Lowmag trial

https://doi.org/10.21203/rs.3.rs-3750227/v1

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Background

Primary tumour biology and axillary lymph node status are crucial prognostic factors in breast cancer treatment. The LowMag trial introduced a magnetic sentinel lymph node biopsy (SLNB) procedure using a Superparamagnetic Iron Oxide (SPIO) tracer and handheld magnetometer as a radiation-free alternative for axillary staging. The objective of LowMag trial was to assess a low-dose magnetic tracer for non-invasive preoperative evaluation of lymph node metastases and intraoperative SLN detection.

Methods

Patients with confirmed invasive breast cancer or ductal carcinoma, eligible for SLNB, were included in the LowMag trial (NTR 4858, http://www.trialregister.nl) consisted of radioactive and magnetic SLNB. The SLNs were perioperatively detected by Sentimag®, and inked to keep track of spatial orientation between MRI and histopathology. Amount of iron was estimated post-surgery using two magnetic devices: SPaQ and Sentimag®. Additional ex vivo MRI was acquired using low-field MRI system (Pure Devices). After buffered in formalin fixation, the LN were lamellated perpendicular to the MRI planes, consecutively sectioned at 2 µm distance and stained with H&E, Perls Prussian blue, CK8/18 and CD68.

Results

In an interim assessment of 20 LNs (nine patients) two LNs from two patients contained a metastasis. The analysis reviled good uptake concordance between magnetic and radioactive tracer with median amount of iron trapped was 19.21 µg (ranging from 0.1 pg to 109 µg). Within healthy LNs, iron particles were observed in both the subcapsular space and sinusoids, with macrophages located in their proximity. Healthy regions within metastatic LNs exhibit a behaviour similar to that of the healthy LNs. In the metastatic sites, there was a reduced presence of iron pigment, particularly in the areas occupied by tumour cells. The healthy LN with low iron content shows a large fatty region in the centre of the node without iron uptake, and confirmed iron in the sinusoidal macrophages. The metastatic LN shows subcapsular and parenchymal tumour cells located in the central region, with limited infiltration into the nearby adipose tissue, without presence of local iron enhancement. However, iron deposits are were detected within the sinusoids.

Conclusion

The MRI images clearly differentiate between fat, nodal tissue and SPIO tracer (either in signal intensity or in texture), demonstrating a potential of LN imaging using a low-field MRI system.

Magnetic SLNB

LN staging

clinical trial protocol

SPIO

MRI

Primary tumour biology and axillary lymph node status are important factors when it comes to prognosis and therapeutic management in breast cancer treatment[1]. Sentinel lymph node biopsy (SLNB) with the dual technique (radioisotope and blue dye) is considered the standard method of axillary staging, both in prior surgery and after neoadjuvant treatment (NAT).

However, the combined method still suffers from disadvantages, such as the use of radioactive materials and the fact that node-positive patients require multiple surgical procedures. Although the radioactive dose is low, the requirement on radioactive tracers leads to complicated logistics and regulations and makes that the sentinel node procedure is out of reach for patients in less developed countries. Besides, for axillary SLNB there is a minor risk of treatment related morbidity, as lymphedema, limitations in shoulder range of motion, loss of strength, numbness, dysesthesias and pain. A major disadvantage especially for the 80% node-negative patients after histopathological examination. [2]

In the conventional SLNB-procedure patients receive standard radioisotope injection 3–24 hours pre-operatively: 2 injections of Tc-99m albumin colloid with a total activity of approximately 50–140 MBq (depending on the time frame). Two hours post-injection of the Tc99-m Nano colloid, conventional planar lymphoscintigraphy is being performed. Blue dye is only administered in case of insufficient transcutaneous signal measured pre-surgery with help of the gamma probe.

A magnetic technique, using a Superparamagnetic Iron Oxide (SPIO) tracer and handheld magnetometer for a radiation free SLNB-procedure was developed and have successfully been investigated in earlier studies to overcome drawbacks associated with the use of radioactivity. [3] [4]

However, accurate imaging in the diagnostic phase could save axillary surgery in 80% of patients without lymph node metastases. Besides, Patients with lymph node metastases (20%) can undergo targeted minimally invasive axillary treatment. Preoperative stratification of patients with tumour-negative axillary nodes, or axillary nodes with a low tumour load that does not warrant further surgery (< 2mm) but guides therapeutic decisions, may allow for a tailored approach without SLNB. [5] In this case, the contrast will be taken up by the lymphatic vessels, reach the SLNs and then be visualized by a radiological modality.

Harinsinghani et al. [6] were the first to demonstrate that intravenously administered Ultrasmall Superparamagnetic Iron Oxide (USPIO) enhanced Magnetic Resonance Imaging (MRI) can be used to non-invasively predict the nodal status of prostate cancer patients. USPIO and Superparamagnetic Iron Oxide (SPIO) particles exert negative contrast on MRI. The uptake of the (U)SPIO particles by macrophages that accumulate in lymph nodes, results in black-appearing nodes on MR-images. In malignancy-baring regions of the lymph node, no macrophages are accumulated and the specific regions keep their original intensity. [7] If imaging can be performed with sufficient resolution, the inhomogeneous reduction of signal in metastatic lymph nodes as compared to the homogenous reduction of signal in nonmetastatic nodes, theoretically allows for the non-invasive preoperative detection of lymph node metastases.

The objective of this study was to assess a low dose magnetic tracer for non-invasive pre-operative evaluation of lymph node metastases (Fig. 1) and intra operative SLN detection.

Patients and trial design

Patients with histologically confirmed invasive breast cancer or ductal carcinoma in situ (DCIS) visible on ultrasound imaging, presented to Medisch Spectrum Twente between August 2021 and August 2023, were considered for the Lowmag trial (NTR 4858, http://www.trialregister.nl). Patients eligible for SLNB[8] (cN0, clinically no metastases in the lymph nodes) and patients with cN1 (proven metastasis after biopsy) undergoing upfront surgery (lumpectomy or mastectomy) and available for a minimum of 12 months follow-up were included in the study. Patients who received neo-adjuvant treatment or who are allergic or hypersensitive to iron or dextran compounds were excluded. Ethics Committee (Medical Research Ethics Committees United, MEC-U Nieuwegein, the Netherlands) approval was obtained before the start of inclusion, and all patients provided written informed consent.

The LowMag trial, investigates the intraoperative detectability of the SLN using a low dose peritumoral SPIO (Magtrace) injection in combination with the SentiMag detection system. Moreover, SPIO-enhanced sequences are being explored to visualize metastases in ex vivo SLN (summarised in Fig. 2). The relevant MRI sequences and processing algorithms are assessed by correlating histopathology with MR images.

Prior to surgery

SPIO injection. The patients receive a peritumorally injection (Fig. 3) of 1 mL (28mg iron) SPIO (Magtrace®, Endomag, Cambridge, UK) within a week prior to surgery. The peritumoral dorsal injection of the SPIO tracer for a magnetic SLNB is placed under Ultrasound guidance by an experienced breast radiologist. The dorsal placement is important to prevent for Susceptibility Artifacts during follow-up MRI, caused by iron remnants[9].

^99m Tc injection and lymphoscintigraphy; In the first study cohort, patients received a standard of care radioisotope injection 3–24 hours pre-operatively: 2 subareolar/subcutaneous injections of Tc-99m nanocolloid with a total activity of max 140 MBq. Two hours after the tracer injection a conventional planar lymphoscintigraphy was performed. In the second cohort the radioactive tracer was omitted.

During the surgery

Sentinel lymph node detection. The SLNs were perioperatively detected by the CE-certified handheld magnetic probe (Sentimag®, Endomagnetics, Cambridge, UK) [10] Fig. 4a). Disposable (plastic) surgical instruments were used during the magnetometer measurements, to prevent for disturbance of the magnetic field. Current-standard-of-care SLNB procedure (involving radioactive tracer and blue dye) was used in case of an unsuccessful magnetic procedure, if no hotspot can be found, or as a control measurement. The magnetometer and gamma counts were documented for all excised sentinel node(s). The residual counts in the axillary region were documented for both the magnetometer and the gamma probe.

Tissue ink for lymph node orientation. Each node was inked with three colours to mark the orientation for correlation between pathology images and MR images. As illustrated in Fig. 5, a half of the node was inked with black colour. Of the remaining half, one part was inked green, and the remaining quarter was inked yellow (The Davidson Marking System ®, Bradley Products, Inc)

After the surgery

Two different devices were used to assess the iron-distribution around the excised LN.

Assessment of iron content by SPAQ. The Super Paramagnetic Quantifier (SPaQ) is an in-house developed magnetometer featuring a sample holder situated within a uniform magnetic field[11] (Fig. 6). SPaQ was employed in its differential magnetometry (DiffMag) mode [12]. The SLN (situated in a glass tube) was placed in an alternating magnetic field generated by an excitation coil to measure the dynamic magnetisation curve. The specific SPaQ settings used involve AC amplitude of 0.83 mT, AC frequency of 2.5 kHz and DC field strength of 4.99 mT [13]. The evaluation was supported by a lookup table (LUT) tailored to quantify the accumulation of the Magtrace magnetic tracer within LN through the utilisation of magnetic readout counts [14].

Figure 6 SPaQ device with a SLN situated in the glass sample holder.

Assessment of iron content by Sentimag. The Sentimag magnetometer operates on the basis of magnetic susceptometry, generating a brief alternating magnetic field that temporarily magnetizes the iron oxide particles present in Magtrace. This magnetic signature, generated by the small amounts of iron, is subsequently detected by the same probe. The magnetic readout counts produced by the Sentimag magnetometer were correlated with the quantity of iron captured within the lymph node (LN) using a specifically tailored Look Up Table (LUT) designed for the Magtrace magnetic tracer^*[15]. The counts, and consequently the trapped amount of iron, were recorded at six distinct orthogonal positions on the surface of the lymph node for each sensitivity setting (1, 2, 3) of the Sentimag as illustrated in Fig. 7. Disposable (plastic) surgical instruments were used during the magnetometer measurements, to prevent for disturbance of the magnetic field.

Ex vivo low-field MRI. The LNs were subsequently imaged using a portable low-field MRI system (Pure Devices GmbH, Rimpar, Germany) with an increased bore of 15mm diameter at a field strength of 0.5T (Fig. 8). The 3D spin-echo images were acquired with a field-of-view 14x14x14 mm and an isotropic resolution of 125µm: Spin echo T1-weighted (T1W), T2-weighted (T2W), short tau inversion recovery (STIR), T1 and T2 maps [Table 1]. Photographs were taken of the LN orientation to ensure comparison with histopathological images. As formalin is the constant element in all MRI images, we have used this to normalise weighted MRI.

Table 1

Low-field table top MRI scan parameters.
	T_1W	T_2W	T_{1W − STIR}
T_R/T_E (ms)	450 / 4.5	4000 / 4	3000 / 4
# averages	8	2	3
FOV (mm³)	14 x 14 x 14	14 x 14 x 14	14 x 14 x 14
Acquisition matrix size	56 x 56 x 56	56 x 56 x 56	56 x 56 x 56
Resolution acquired (mm)	0.25	0.25	0.25
Resolution reconstructed (µm)	125	125	125
Acquisition time (min)	47.91	39.71	60.57

Histopathology examination. After buffered in formalin fixation, the three-coloured LN were lamellated at 250µm distance perpendicular to the MRI planes and enclosed in a cassette for further histopathological processing. Each cassette potentially contained more than one lamella. The embedded lamella was sectioned with the microtome at 2 µm distance and stained with H&E, Perls Prussian blue, CK8/18 and CD68. Figure 9 shows an overview of this procedure. The slides are scanned with Phillips' IntelliSite Ultra-Fast Scanner. For the histopathological analysis of sentinel nodes, each harvested LN was assessed on presence of iron, fat, macrophages and metastases by an experienced pathologist using a semiquantitative quaternary (0–3+) scale, resulting in a pT stage.

In the histopathology images, the pathologist conducted a comparative analysis across all four stains for a number of relevant regions of interest (ROIs). The focus was on establishing correlations between macrophages (CD68 stain), metastases (CK8-18 marker), and iron accumulation (Perl’s Prussian Blue stain). Particular emphasis was on evaluating disparities between metastatic and non-metastatic regions within LNs containing metastases, as well as distinctions between non-metastatic regions in LNs with and without metastases.

Patients and magnetic SLNB

In an interim assessment, the initial nine patients undergoing the extensive histopathology and MRI protocol were analyzed with the intention of refining the protocol. All nine participants were female with a mean age of 59.6 years (52–68). They received a peritumoral injection on either the latero cranial or dorsal side of the tumor. The average duration between injection and resection was 3.2 days, ranging from 1 to 8 days.

Sentinel lymph node detection.

A total of 20 LN was resected, with the number per patient ranging from one to five. Table 2 illustrates patient characteristics including number of LN resected and corresponding amount of iron trapped. Most of the lymph nodes (n = 12) had an uptake of both the magnetic and radioactive tracer. Three lymph nodes had uptake of only the magnetic tracer and one lymph node exclusively absorbed the radioactive tracer (Fig. 10).

Eight out of nine procedures could be performed using only the magnetic SLNB procedure. In one case, the radioactive procedure was used as a backup. Transcutaneous detection of the magnetic tracer was inadequate in almost all cases, once the incision was made through the skin, adequate signals were detected.

Assessment of iron content

Using SPaQ; We found median amount of iron over all 20 LN of 19.21 µg (ranging from 0.1 pg to 109 µg). On average, SLNs contained 0,1% iron of the total injected dose (1ml = 28 mg) ranging up to 0.39%. The iron content in the metastatic LN was non-significantly higher than iron content in non-metastatic LN (Fig. 11-A).

Using Sentimag; When examining the iron content at the six specified positions along the LN surface (illustrated in Fig. 6 by using Sentimag), we observed a significant variation in iron distribution throughout as illustrated in Fig. 11-B for two individual LNs one with metastases and one without metastases. In this specific case, there is significantly more iron with a larger spread in the LN containing metastasis compared to a LN without metastasis. Similar distribution of iron was evident across all three sensitivity settings of Sentimag, irrespective of the presence of metastasis in the lymph nodes.

It's noteworthy that the iron content determined through the Sentimag substantially overestimates the iron content measured using SPaQ (Fig. 11-C).

Histopathology

During the histopathological evaluation, metastasis was identified in two LNs from two patients (see Table 2). Patient 7 exhibited a macro metastasis exceeding 2mm, while patient 5 had a micro metastasis of 0.2-2mm. Additionally, Patient 1 displayed two LNs with isolated tumour cells, each measuring less than 0.2mm.

Within healthy LNs, iron particles were observed in both the subcapsular space and sinusoids, with macrophages located in their proximity (Fig. 12-AB). Similarly, in the healthy regions within metastatic LNs exhibit a behaviour similar to that of the healthy LNs (Fig. 12-C-E). However, in the metastatic sites, there was a reduced presence of iron pigment, particularly in the areas occupied by tumour cells. Additionally, adipose tissue exhibited lower levels of iron accumulation compared to the healthy LN tissue.

Below; Pathology image of a lymph node with a macro metastasis stained with Perl’s Prussian Blue. C) A large iron deposition is found in the healthy glandular tissue (dark pink on the underside). E) There is no iron visible in the tumor tissue (light pink at the top of the lymph node).

The comparative ROI to validate the hypothesis that macrophages are involved in the uptake and transport of iron tracer within the node, the staining on CD68 and FE was compared. In the case of both macro and micro metastasis, no iron was observed in the tumor-bearing regions. Additionally, in regions where iron pigment was identified, macrophages were also visible in the CD68 staining (Fig. 13).

Lowfield MRI

Figure 14 illustrates the MRI of the central slice alongside with the pathology images: healthy LN with low (first row) and high (second row) iron content alongside with a metastatic LN with high iron-content (third row). As expected, regardless amount of iron trapped and the MRI sequence, there were no significant differences between signal intensities for plastic holder and formalin between the samples. All fat regions, regardless metastatic status, show no signs of iron deposition and no significant difference in formalin normalised MRI. The healthy LN with low iron content shows a large fatty region in the centre of the node without iron uptake, and confirmed iron in the sinusoidal macrophages. The metastatic LN shows subcapsular and parenchymal tumour cells located in the central region, with limited infiltration into the nearby adipose tissue, without presence of local iron enhancement. However, iron deposits were detected within the sinusoids.

As 80% of SLNB procedures are deemed clinically unnecessary [2], it imposes avoidable morbidity on these patients. Similarly, to previous recommendations for omitting axillary

lymph node dissection in a substantial number of patients [16], responsibly averting unnecessary LN resection through non-invasive preoperative LN staging promises significant individual healthcare advantages. The LowMag protocol allows for the development and initial validation of preoperative SPIO-enhanced MRI staging prior to breast cancer to prevent for unnecessary LN resection.

We observed an average iron content of 0.1% of the injected dose (1 ml SPION = 28 mg Fe) in the SLNs, ranging from 0–0.39%. This finding is similar to earlier a pilot studies: i.e. the tracer uptake of 0.36% for a 22.4 mg SPION injection in head and neck cancer[17], and 0.3% for a 1.6mL (44.6mg iron) SPION tracer (Resovist) in breast cancer [18].

Earlier studies on visual analysis of axillary LNs in breast cancer patients, using the disparity in MRI signal between before and after SPION injection [19], showed potential in detecting macro metastases. However, visual analysis still presents a potential challenge in terms of consistency among observers. Our previous work [20] and this LowMag protocol attempt to solve this issue by quantifying the MRI of metastatic LN tissue.

The MRI images clearly differentiate between fat, nodal tissue and SPIO tracer (either in signal intensity or in texture), demonstrating a potential of LN imaging using a portable MRI scanner at 0.5T. However, given the long acquisition time, the scan protocol needs significant time reduction before implementation in clinical setting and pre-operative in vivo scan protocol. Compressed sense reconstruction seems suitable for this purpose[21].

Previous study results of the Lowmag trial showed that patients with fatty SLNs (without metastases) only show SPIO uptake in the cortex. Not in or between fat cells. These SLN showed a thickened cortex after SPIO injection and appeared totally black in the fat-suppressed images. Therefore fat- and water- only images (STIR/DIXON) were used for the distinguish between fatty and metastatic LN.

The dispersion of the tracer through the lymphatic system and its uptake in the SLNs is potentially influenced by the injection method (injection site, dose, and timing). Additionally, residual SPIOs at the injection site potentially result in void artifacts in follow-up MRI examinations in near proximity of the injection spot[22]. This information on tracer uptake in SLNs can be valuable for dose and protocol optimization.

The LowMag protocol holds promise to facilitate development of tools in supporting a comprehensive approach, where axillary surgery is reserved for patients with confirmed metastatic lymph nodes.

Author Contribution

All authors contributed to the development of this study protocol and provided input within their respective specialties (see below). AC (technical physician) acted as the study coordinator and drafted the initial version of the manuscript. AD (surgical oncologist) served as the principal investigator of the study and primary caregiver for the patients. AD oversaw the surgical aspect of the study and the manuscript. MS (radiologist) was responsible for the radiology component of the study and the manuscript. MB (pathologist) oversaw the pathology section of the study and the manuscript. SS (university lab manager) was responsible for the measurements and adherence to protocols (Fe counts and MRI sequences). BtH and LA were founders of the study. LA provided the manuscript with an initial revision. All authors reviewed the last version of the manuscript.

Kim MK, Park HS, Kim JY, Kim S, Nam S, Park S, Kim SI: The clinical implication of the number of lymph nodes harvested during sentinel lymph node biopsy and its effects on survival outcome in patients with node-negative breast cancer. Am J Surg 2017, 214(4):726-732.
Giammarile F, Vidal-Sicart S, Paez D, Pellet O, Enrique EL, Mikhail-Lette M, Morozova O, Maria Camila NM, Diana Ivonne RS, Delgado Bolton RC et al: Sentinel Lymph Node Methods in Breast Cancer. Semin Nucl Med 2022, 52(5):551-560.
Douek M, Klaase J, Monypenny I, Kothari A, Zechmeister K, Brown D, Wyld L, Drew P, Garmo H, Agbaje O et al: Sentinel node biopsy using a magnetic tracer versus standard technique: the SentiMAG Multicentre Trial. Ann Surg Oncol 2014, 21(4):1237-1245.
Karakatsanis A, Christiansen PM, Fischer L, Hedin C, Pistioli L, Sund M, Rasmussen NR, Jornsgard H, Tegnelius D, Eriksson S et al: The Nordic SentiMag trial: a comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc(99) and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies. Breast Cancer Res Treat 2016, 157(2):281-294.
Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L et al: Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol 2014, 15(12):1303-1310.
Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH, de la Rosette J, Weissleder R: Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003, 348(25):2491-2499.
Cheng G, Kurita S, Torigian DA, Alavi A: Current status of sentinel lymph-node biopsy in patients with breast cancer. Eur J Nucl Med Mol Imaging 2011, 38(3):562-575.
Richtlijnendatabase [https://richtlijnendatabase.nl/richtlijn/borstkanker/dcis/swk_biopsie.html]
A Christenhusz MvS, B ten Haken, L Alic, AE Dassen: Preventing Postoperative Susceptibility Artifacts caused by iron remnants: Managing image guided injection site. In: EUSOBI: 28-30 September 2023 2023; Valencia, Spain; 2023.
Sentimag [https://www.endomag.com/products/sentimag/]
van de Loosdrecht MM, Draack S, Waanders S, Schlief JGL, Krooshoop HJG, Viereck T, Ludwig F, Ten Haken B: A novel characterization technique for superparamagnetic iron oxide nanoparticles: The superparamagnetic quantifier, compared with magnetic particle spectroscopy. Rev Sci Instrum 2019, 90(2):024101.
S. Waanders MV, T.O.B. Oderkerk, H.J.G., Krooshoop aBtH: Method and apparatus for measuring an amount of superparamagnetic material in an object. In: Espacenet. Edited by Twente Uo, G01N27/72 edn. The Netherlands; 2015: 11.
Molenaar L, Loosdrecht MMHvd, Alic L, Baarlen Jv, Meijerink JJHJ, Haken Bt, Broeders IAMJ, Lips DJ: Quantification of Magnetic Nanoparticles in ex vivo Colorectal Lymph Nodes. Nano LIFE 2022, 12(03):2250006.
Molenaar L: Look-up table based on SPaQ measurements to quantify amount of iron in small samples. In., 1 edn. 4TU.ResearchData; 2021.
Sadaf Salamzadeh AC, Lejla Alic: Look-up table for assessment of iron content in Magtrace® samples based on Sentimag® In. 4TU.ResearchData: University of Twente, Faculty of Science and Technology, Magnetic Detection & Imaging (MDI) Group; 2023.
van der Noordaa MEM, Vrancken Peeters M, Rutgers EJT: The intraoperative assessment of sentinel nodes - Standards and controversies. Breast 2017, 34 Suppl 1:S64-s69.
Nieuwenhuis ER, Kolenaar B, Hof JJ, van Baarlen J, van Bemmel AJM, Christenhusz A, Scheenen TWJ, Ten Haken B, de Bree R, Alic L: A Comprehensive Grading System for a Magnetic Sentinel Lymph Node Biopsy Procedure in Head and Neck Cancer Patients. Cancers (Basel) 2022, 14(3).
Sekino M, Kuwahata A, Ookubo T, Shiozawa M, Ohashi K, Kaneko M, Saito I, Inoue Y, Ohsaki H, Takei H et al: Handheld magnetic probe with permanent magnet and Hall sensor for identifying sentinel lymph nodes in breast cancer patients. Sci Rep 2018, 8(1):1195.
Motomura K, Ishitobi M, Komoike Y, Koyama H, Noguchi A, Sumino H, Kumatani Y, Inaji H, Horinouchi T, Nakanishi K: SPIO-enhanced magnetic resonance imaging for the detection of metastases in sentinel nodes localized by computed tomography lymphography in patients with breast cancer. Ann Surg Oncol 2011, 18(12):3422-3429.
A Christenhusz FS, N de Vries, M Hofman, AE Dassen, B ten Haken, L Alic. : Potential of MR lymphography for LN staging in breast cancer. In: European Congress of Radiology. 2021.
Arthur de Lange LA, Bennie ten Haken, and Frank F.J. Simonis: Accelerated imaging of resected lymph nodes at high spatial resolution using a portable low-field MRI scanner. In: ISMRM: 2023; Toronto Canada; 2023.
Christenhusz A, Pouw JJ, Simonis FFJ, Douek M, Ahmed M, Klaase JM, Dassen AE, Klazen CAH, van der Schaaf MC, Ten Haken B et al: Breast MRI in patients after breast conserving surgery with sentinel node procedure using a superparamagnetic tracer. Eur Radiol Exp 2022, 6(1):3.

* http://ironcalculator.utwente.nl/

Table 2 is available in the Supplementary Files section.

No competing interests reported.

Table2.docx

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Journal Publication

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Magnetic procedure for sentinel lymph node detection and evaluation of metastases: Design and rationale of the Lowmag trial

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Introduction

Methods

Patients and trial design

Prior to surgery

During the surgery

After the surgery

Results

Patients and magnetic SLNB

Assessment of iron content

Histopathology

Lowfield MRI

Discussion

Declarations

Author Contribution

References

Footnotes

Table 2

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1