Key words MR-guided interventions - MR-guided biopsy - MR-guided ablation - HIFU
Introduction
Interventional MRI is already part of the clinical routine for many areas of application
such as breast and prostate biopsy as described in detail in the first part of this
overview [1 ]. Because of the ability to clearly visualize tumor borders and to image the effects
achieved by tumor ablation, this method is particularly important in the treatment
of oncology patients. For comprehensive inclusion of the method in the clinical routine,
it is still necessary to determine whether cost coverage can be ensured. All aspects
of DRG billing must be included in such an analysis. This overview first describes
interventional MRI methods and current fields of indication. MR-guided focused ultrasound
is also taken into consideration here. A cost/reimbursement analysis showing cost
coverage is performed at the end of the article on the basis of oncological application
areas (MR-guided tissue ablation). Based on this, interventional MRI should be increasingly
included in the clinical routine.
Instruments and operating concepts for oncology
Instruments and operating concepts for oncology
The number of findings diagnosed on the basis of MR imaging in oncology patients and
the options for the molecular characterization of tumors are increasing. Thus, the
need to perform percutaneous interventions under MRI guidance is also increasing.
In addition to use in the simple biopsy of tissue samples and aspirations [2 ]
[3 ]
[4 ]
[5 ]
[6 ]
[7 ]
[8 ], MR-guided treatment types such as sclerotherapy [9 ]
[10 ], targeted injections [11 ]
[12 ]
[13 ], drainage [14 ]
[15 ] and local tumor treatment [16 ]
[17 ] have been described.
The first part of this overview discussed the freehand technique in open MRI [1 ]. Unfortunately, these horizontally open scanners are much less available than closed
MRI scanners. The simplest way to perform interventions on a cylindrical MRI scanner
is the single-step procedure as used in CT-guided interventions. To determine the
location of a lesion and to monitor needle position, the patient must be moved into
the isocenter of the MRI scanner and then moved back out of the scanner for incremental
advancement of the needle using the freehand technique [2 ]
[6 ]. The interventions specified above require needles for aspiration, injection and
biopsy that are visible on MRI, laser applicators, RF electrodes, and microwave antennas
for ablation that are available from multiple manufacturers. The size of the instrument
artifact depends among other things on the material, the magnetic field, and a series
of sequence parameters. Therefore, individual adjustment of the parameters is essential.
In addition to suitable instruments, a shielded monitor is needed in the magnet room
and is commercially available both for 1.5 T and 3 T MRI scanners. A series of tools
have been developed to facilitate interventions in very narrow and long cylindrical
magnets. For example, a control grid that is visible on the MRI image and allows a
stereotactic approach has become established for breast biopsy [2 ]. MR-compatible robotic assistance systems intended to facilitate instrument placement
in the magnet are more technically complicated [18 ]
[19 ]
[20 ]. Moreover, needle guides using augmented reality (AR) to project information acquired
by the MRI scanner onto the patient lying directly in front of the magnet have been
introduced [21 ]
[22 ]
[23 ]. Both robotic and AR systems are currently only used as prototypes and are not yet
commercially available.
Compared to the stepwise approach with and without additional support systems, continuous
imaging during MR-guided puncture in the "open" magnet has significant advantages.
Puncture under real-time control is possible because most cylindrical MRI scanners
have become shorter and have large openings (> 70 cm) that allow access to the patient
in or near the isocenter of the magnet and advancing of the needle under continuous
MRI guidance [8 ]
[13 ]
[24 ]. This is also possible in the case of open MRI scanners with 2 horizontally arranged
magnetic poles that allow good access to the patient depending on the diameter of
the poles and the size of the opening between the poles. In the case of a small pole
diameter, access is good but the quality of the almost real-time imaging is limited
due to the low field strength of these systems [14 ]
[25 ]. Horizontally open MRI scanners with higher field strengths provide higher image
quality [12 ] but commercial availability is currently still limited. Regardless of the system
design, MR imaging in real time in "open" magnets during puncture has several advantages:
the free selection of slice orientation in MRI can be interactively used with the
help of a water-filled syringe or a finger to find the body access point without a
light localizer and/or marker; continuous imaging of the needle, puncture path, and
target allows safe puncture; oblique puncture trajectories can be better maintained
in the freehand technique; efficient puncture is possible [2 ]
[4 ]
[13 ]
[26 ]. Ideally the interactive adjustment of slice planes does not have to be performed
manually but rather fully automatic adjustment to the orientation of the instruments
is performed [27 ]. To facilitate needle tracking, interactive user interfaces for MR-guided interventions
have been introduced [4 ]
[27 ]
[28 ] some of which can also process coordinates from external navigation systems to adjust
the slice orientation to the trajectory of the instrument. Moreover, efforts are being
made to integrate instrument navigation, ablation planning software, and temperature
monitoring into the MRI scanner to achieve an integrated approach to tumor treatment.
The goal is to create a user interface with which a tumor can be punctured under MRI
guidance in such a targeted manner that simulation predicts destruction with a safety
margin. This plan is then compared to temperature measurements in real time to ensure
complete ablation with a safety margin (A0 ablation).
In summary, a number of tools and user interfaces are available for conducting percutaneous
interventions under MRI guidance. Some of the presented methods have already proven
their value in clinical use. The improvement of the interactive user interface and
the development of intuitive operating concepts will further simplify workflows during
MR-guided puncture and ablation so that these procedures can be performed even more easily
and safely.
Thermal ablation methods (LITT, RFA, MWA, CA) and noninvasive temperature measurement
for monitoring results
Thermal ablation methods (LITT, RFA, MWA, CA) and noninvasive temperature measurement
for monitoring results
Minimally invasive thermoablation treatments including laser-induced thermal therapy
(LITT), radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation
(CA) have become established as efficient and precise methods for the coagulation
of various tumors and have been used for a number of years in the clinical routine.
According to the literature, the use of these methods for tumor treatment achieved
median survival rates of 33.7 (LITT), 33.2 (RFA) and 29.5 (MWA) months [29 ] and a positive response rate of 98.2 % (LITT), 97 % (RFA) and 62.5 % (MWA) [30 ].
Compared to other imaging methods, MRI is characterized by superior soft tissue contrast,
multiplanar visualization, and a lack of ionizing radiation. As a result of the adequate
differentiation and visualization of soft tissues, MRI is becoming increasingly important
in early diagnostic imaging. An additional, albeit but not unique, advantage is that
MRI is a completely noninvasive treatment monitoring method. As a result of such MR-guided
monitoring methods, online display of the coagulation region and the temperature change
can be achieved allowing better planning of any necessary repositioning of the transducer
and thus control of the entire thermoablation treatment. Moreover, MR-compatible applicators
for use in LITT, RFA, MWA, and CA methods under MRI guidance have been developed in
recent years. Precise clinical data and broad experience regarding these MR-guided
methods are already available [31 ]
[32 ]
[33 ]
[34 ]
[35 ]
[36 ].
MR thermometry is currently the most successful noninvasive method for temperature
monitoring during treatment. An ablation procedure can be controlled based on temperature-dependent
MRI parameters, such as proton resonance frequency (PRF), spin-lattice relaxation
time (T1), diffusion coefficients, and the chemical shift of an exogenous sample ([Fig. 1 ]). The PRF method is preferred due to its independence from tissue type and its robustness
[36 ]
[37 ]. The PRF method is based on the temperature-dependent phase change that allows calculation
of the temperature difference (in relation to the phase position in the reference
image prior to heating). As a result of real-time MR thermometry, the temperature
change achieved during treatment can be determined and the size and position of the
coagulation region can be verified. However, MR thermometry is currently limited by
the relatively long acquisition time of several minutes on the MRI scanner and artifacts
in moving organs. The literature reports temperature accuracy of approx. 0.2 °C for
in-vivo measurement in the brain [36 ], 2 °C for in-vivo measurement in the liver [38 ] and 0.7 °C for ex-vivo measurement in pig liver [37 ].
Fig. 1 MRI basel temperature measurement during LITT in a gel phantom. Temperature is coded
by different colors. The image has been acquired with an echo planar imaging (EPI)
sequence.
Due to the greater demand for thermal ablation methods, further development and improvement
of MR thermometry is desirable for optimal treatment control. This will result in
an increase in patient safety and thus in long-term use of thermotherapy methods in
the clinical routine.
Focal therapy of prostate cancer
Focal therapy of prostate cancer
MR-guided methods for focal therapy of prostate cancer, especially laser ablation,
cryotherapy, and focused ultrasound, are becoming a promising option for treating
low-grade to medium-grade tumors as an alternative to active monitoring and prostatectomy.
Targeted treatment of the index tumor while protecting sensitive neighboring structures
makes it possible to reduce treatment-associated side effects such as erectile dysfunction
and incontinence [39 ].
The safety and feasibility of the indicated methods was able to be proven in various
phase I studies with a low side effect profile in each case [40 ]
[41 ]
[42 ]
[43 ]
[44 ]
[45 ]. In addition, further studies (evidence level < 2b) with short to medium-term follow-up
intervals of 6 – 12 months were able to show complete tumor ablation for laser ablation
in approx. 75 % of cases and for focused ultrasound in approx. 83 % of cases [46 ]. At the same time, initial study results show that tumor relapse after radiotherapy
or prostatectomy can be treated relatively safely with cryotherapy [47 ]. For example, 7 of 10 patients were tumor-free after 12 months in one study [48 ].
The advantages of MRI compared to ultrasound (US) or MRI-US fusion for intervention
control can be summarized in four points: 1. Targeted preinterventional patient selection
via multiparametric MRI and exact (re-) identification of the index lesion. 2. Accurate
placement of the ablation tools in the target lesion virtually in real time. 3. Real-time
visualization of the coagulation region for complete selective tumor ablation via
MR thermometry during laser ablation or via focused ultrasound or T1-weighted sequence
during cryotherapy (monitoring). 4. Direct review and documentation of ablation results
after final contrast agent administration (monitoring of results).
The disadvantages of MRI are the comparatively high cost and the long intervention
times of approx. 1 – 6 hours [41 ]
[45 ]. A reproducible reduction of the intervention time to less than three hours would
make greater use of focal therapy in the clinical routine more realistic. MR-compatible
robotic systems for automated intervention control could contribute to this [49 ].
MR-guided focal therapy has achieved good results and provides a possible solution
to a central problem in the current treatment regime, i. e. the overtreatment of low-
and medium-grade prostate cancer. For focal therapy to be able to become established
in the future as an alternative, studies over longer periods and involving larger
groups of patients are needed.
MR-guided focused ultrasound
MR-guided focused ultrasound
MR-guided focused ultrasound (MR-HIFU, MRgFUS) has been available for clinical application
in various diseases for more than 10 years. The basic idea is to focus ultrasound
waves from multiple sources on one point in the body thus transferring very high energy
to the target region. Systems with several hundred elements that have a slightly lower
frequency (approximately 1 MHz) compared to diagnostic ultrasound but achieve a significantly
higher average intensity (up to 10 000 W/cm2 ) in the target volume are typically used [50 ]. Maximum penetration depths of up to 15 cm can be achieved with currently available
systems. The most important effect of focused ultrasound is the local heating of the
tissue in the target region with coagulation necrosis occurring starting at a temperature
of approximately 60 °C. In addition, there are also mechanical and chemical effects
that can be used in different applications.
In principle, treatment can also be performed under ultrasound guidance. However,
the use of MRI has definite advantages. On the one hand, three-dimensional MR imaging
in combination with the excellent soft tissue contrast makes it possible to determine
the exact location of the target lesion. On the other hand, direct treatment control
and targeted treatment guidance can be achieved by MR thermometry. The definite advantage
compared to all other interventional methods for local destruction of tissue is that
needles and catheters are not necessary and the integrity of the body surface is maintained.
The most established and best evaluated application of MR-HIFU is the treatment of
uterine fibroids ([Fig. 2 ]). Treatment takes approximately 2 to 3 hours, can be performed on an outpatient
basis under analgosedation and most patients can usually resume normal activities
the following day [51 ]. The method has undergone further technical development in recent years to improve
safety and efficiency [52 ]
[53 ]. Clinical studies show that the results are comparable with other uterus-preserving
treatment methods [54 ]. In the meantime, other benign tumors (e. g. fibroadenomas, osteoid osteomas) have
also been successfully treated with focused ultrasound [55 ].
Fig. 2 Contrast enhanced T1-weighted sequence with fat saturation prior A and after B HIFU. The large myoma centrally within the uterus enhances prior treatment. After
therapy the non-enhancing areas of approximately 85 % of the myoma volume, correspondes
to coagulation-necrosis.
Based on experience treating benign tumors, there are now numerous experimental studies
and small patient series regarding the treatment of malignancies [56 ], in particular, pancreatic tumors, breast cancer, prostate cancer, renal tumors,
liver tumors, and brain tumors. A further oncological application that is possible
with currently available systems is the treatment of bone metastases [57 ]. However, in this application, not the complete destruction of the tumor but rather
the treatment of pain in the palliative situation is the first priority.
In the applications described to date, focused ultrasound is always used for the direct
destruction of the tissue in the target region. There are numerous additional possible
therapeutic applications. For example, local hyperthermia can be generated in malignant
tumors by means of HIFU to increase sensitivity to radiation or chemotherapy.
A further approach is the use of HIFU effects for the local application of medications
[50 ]. For example, thermosensitive liposomes that release the medication contained in
the liposomes in the target region in the case of mild hyperthermia without thermal
damage to the tissue can be used for this purpose. Another approach uses the mechanical
properties (acoustic cavitation) of ultrasound waves to temporarily increase the permeability
of cell membranes (sonoporation). A clinically interesting application is the temporary
opening of the blood-brain barrier, as has been able to be successfully performed
in animal experiments, to apply, for example, dopamine receptor antibodies or chemotherapeutic
agents in a targeted manner.
Financial feasibility of MR-guided interventions
Financial feasibility of MR-guided interventions
Status analysis
The challenge regarding oncological interventions under MR guidance (iMRI) is that
operating the MRI system alone or as a hybrid system initially results in an increase
in primary and secondary costs compared to conventional methods in angiography, ultrasound,
and computed tomography. However, the method provides better soft tissue contrast
and can be directly combined with excellent functional imaging. For this reason, the
procedure for performing MR-guided interventions cannot be simply transferred from
current standard concepts in interventional radiology but rather must be based on
general conditions such as the case mix index of the disease, the complexity of the
treatment concept, and billing using numbers from comparable medical services.
Therefore, oncological interventions such as interventional thermoablation and navigation-assisted
implantation of radioactive iodine seeds are suitable particularly for iMRI with cost
coverage.
Calculation using oncological interventions as an example
Organization
To ensure efficient utilization of an MRI system, it is ideal to combine periodically
performed interventions with corresponding diagnostic imaging covered by reimbursement.
Calculations have shown that use of the system for interventions 2 days a week in
combination with planning and follow-up imaging on the other days results in amortization
of the innovation costs over a period of 8 – 10 years in a conservative analysis with
slow dynamics of development with gradual doubling times over multiple years. It must
be assumed that the dynamics depend on the strategic business model that develops
over the course of the years from the continuation of the medical indications on the
one hand and the influx of innovations on the other hand. This continuous influx of
innovations ideally results from a test environment established in parallel to clinical
iMRI to prevent downtime. An example of this is the research campus M2OLIE in Mannheim
at which a clinical iMRI suite as well as a purely experimental intervention suite
are set up to develop and test technical innovations in the field of navigation and
robotic assistance systems in a targeted manner.
In addition to usage times, the expenses for infrastructure must be calculated. These
can be divided into conversion costs, personnel costs for physicians and medical-technical
personnel, and ongoing costs for power and maintenance. In the above usage model,
these costs can be shown within the targeted refinancing period of 8 – 10 years. The
system must be used in a regulated manner for the individual treatment units and diagnostic
examinations for preparation, monitoring, and follow-up to ensure efficient use of
these resources and to prevent longer idle times of the iMRI system.
Procedures
For the above refinancing, oncological interventions using minimally invasive ablative
procedures (thermoablation, irreversible electroporation, IRE, etc.) are particularly
suitable since these can be represented as partial organ resection. Interventions
involving the kidney such as ablation of renal cell carcinomas in inoperable patients
or patients with a single kidney, ablation of bronchial carcinomas up to a size of
approx. 2 cm with a curative intent or ablation of lung metastases to stabilize patients
with oligometastases are particularly relevant to reimbursement. In contrast, interventions
involving the liver are less cost-covering since the reimbursement is usually significantly
less than the material costs of the thermoablative methods used.
With respect to other concepts for minimally invasive tumor therapy, cooperative interdisciplinary
models are important for targeted optimization of the reimbursement structure. An
increasingly common indication is the interventional implantation of radioactive iodine
seeds in cooperation with radiotherapy/radiation oncology. In iMRI, these methods
can be used alone, e. g. for the prostate or in the case of unresectable recurrent
rectal cancer in the small pelvis, to increase precision regarding the coverage of
the clinical target volume, or in combination with radiological interventional thermoablative
methods in multifocal lesions with a partially infiltrative growth pattern, e. g.
in cholangiocellular carcinomas with intrahepatic metastases. It is important for
the compensation structure that brachytherapy in the region of the pelvis is able
to be billed analogously to conventional radiotherapeutic methods and the added technical
costs for increasing precision by means of iMRI can be covered.
Consideration of future developments
To ensure refinancing of the iMRI system possibly as a hybrid suite with an additional
angiography system over the long term, it is important for radiology to be positioned
as an equal clinical partner in an innovative clinical oncological environment in
the context of patients with oligometastases to ensure a continuous flow of patients
in radiology in cooperative models. In addition to the purely case-based reimbursement
values, interdisciplinary treatment of oncological diseases in the stage of oligometastases
results in an increasingly complex patient spectrum that can be potentially represented
in the case mix index and in the corresponding DRG flat rates. The following shows
a patient with prostate cancer and a liver metastasis to be ablated with a length
of stay of 3 days as an example:
Ablation – liver (length of stay: 3 days):
Diagnoses: Secondary malignant neoplasm of liver (C78.7), malignant neoplasm of prostate
(C61)
Procedures: 5 – 501.53, CT/MRI
DRG H41C, CMI = 1.604
At present, this is reimbursed at an amount of 4536.12 € in Baden-Württemberg.
In contrast, the optimization of iMRI systems or combined hybrid suites with respect
to supporting hardware and software for navigation, the integration of assistance
systems and data fusion can require the integration of multiple manufacturers to create
innovative individual components. The expenditure including downtime and personnel
for creating interfaces or addressing regulatory aspects in accordance with the Medical
Device Directive can result in significant costs that can be difficult to calculate.
Manufacturers are requested to search for integrative solutions in cooperative models
as, for example, in the case of the development environments M2OLIE (Mannheim) and
STIMULATE (Magdeburg/Hannover) of the research campuses that make possible major initiatives
of the Federal Ministry of Education and Research.
Developments for a general cost reduction of iMRI
The use of iMRI is expected to result in a reduction in morbidity due to the more
precise and gentle interventions with potential shortening of the length of stay in
the short term and in a reduction of interventions in case of relapse due to improved
soft tissue contrast in the medium to long term. The shortening of the length of stay
frees up resources for treating additional patients In particular, simplification
of the spatially limited options regarding navigation in iMRI or shortening of the
current navigation times in hybrid suites using complicated X-ray equipment will result
in an increase in efficiency. One possibility here is the use of ultrasound systems
with which a majority of real-time interventions could be performed outside the iMRI
system using image fusion on the basis of MRI image data acquired before and after.
Conclusion and outlook
Interventional MRI is established for diagnostic imaging for many indications in patients
with suspicion of a malignancy. It is comprehensively used for breast biopsy and is
being increasingly used for prostate biopsy. Decisions regarding biopsy of other organs,
such as the liver, are typically made on a case-by-case basis when other modalities
are difficult or impossible to use. Interventional MRI offers unique advantages for
image-guided ablation due to the exact visualization of tumor borders and temperature
sensitivity. The cost analysis for the treatment of tumors and metastases shows that
interventional MRI can be performed in a cost-covering manner also in this application
area. This is an important requirement for broader use.
