Description
of technology
Positron Emission Tomography combined with
Magnetic Resonance Imaging (PET-MRI) is an emerging technology recently
proposed to be used in oncology, neurology and cardiology for diagnostic
purposes. The market offers three different PET-MRI systems, developed by three
manufacturers (GE, Philips and Siemens). The GE system - "Trimodality
PET-CT + MR" – is able to capture and correlate PET, CT and MR images
based on two separate devices, a PET-CT and a MRI. The Philips system –
“Ingenuity TF” - has PET and MR gantries arranged in the direction of the main
scanner axis with a patient handling system mounted between the gantries.
Siemens has developed a fully integrated PET-MRI system – Biograph mMR - with
simultaneous acquisition with a single gantry. This is the only system capable
of simultaneously acquiring the image PET-CT and MR, instead the other two systems use special
software to merge the two types of images. In oncology the expected benefits
include the improvement of diagnostic accuracy compared to PET-CT, especially
for soft tissue cancers, with a lower radiation exposure.
Clinical
relevance and burden disease
We can hypothesize the diagnostic application
for some cancers, such as primary brain tumours, carcinoid tumours, prostate
and uterine cancer, because they were objects of few feasibility studies in the
first half of 2000 years where PET and MR images were combined through fusion
of computerized records after separate data acquisition (Cuerva Carvajal 2007).
Outside the oncologic field post acquisition PET and MR imaging fusion has been
applied in one small study for pre-operative assessment of children with
tuberous sclerosis in order to better identify epileptogenous tuberosities for
selection of surgical treatment (Cuerva Carvajal 2007). In synthesis, thus far
no precise disease emerges to profit by the application of combined PET-MRI
images, and so it is impossible to identify any target disease and any clinical
need to be covered with the application of this new technology.
Various sectors of diagnosis are sure to benefit from a hybrid system MR / PET in neurology cardiology, oncology and functional imaging.
Manufacturers
and traders trust company
The market offers three different PET-MRI
systems, developed by GE, Philips and Siemens.
GE has "Trimodality PET-CT + MR", a
system able to capture and correlate PET, CT and MR images. The system proposed
by GE is made up of two separate machines, a PET-CT (Discovery PET-CT 690) and
a 3 Tesla MRI (Discovery MR 750), placed in two separate rooms and connected
together via a mobile patient table on rails (Patient Transfer Discovery table)
which allows the patient to transfer from one modality to the other without
moving from the table. The system is therefore based on the acquisition of
separate PETCT and MRI images, then processed together through a fusion
software managed by the operator through the “Advantage” workstation. The
error as a result of this transfer is about 5mm.
The serial non-hybrid MR / PET of GE Trimodality PET-CT + MR.
Philips system is composed by a 3 Tesla MR and
a PET Time of Flight based. It has PET and MRI gantries arranged in the
direction of the main scanner axis with a patient handling system mounted
between the gantries. The PET was placed coaxially at a distance of 4.2 m from the MRI
(distance between centers of FOV); magnet type is Superconducting 3T;
maximum FOV (cm) 50 × 50 × 45 (MRI) and Axial FOV 18 cm (PET). The
Time of Flight technology allows to make fast acquisitions (5 minutes
examination) and to infuse the patient with a very low dose of
radiopharmaceutical.
The serial hybrid modality MR / PET of Philips Ingenuity TF.
Siemens has developed a fully integrated
PET-MRI system with simultaneous acquisition with a single gantry: PET
detectors integrated into the bore of the MRI. It enables the precise alignment
of MRI and PET by performing both scans at the same time. The magnet type is
Superconducting 3 Tesla. This integrated system uses a non-magnetic
detection technology based on Avalanche PhotoDiode (APD). Such technology is
not optimal for a PET tomograph and prevents the use of Time of Flight.
Further solid state technologies are being studied that will allow to develop
PET/MRI tomographs without sacrifice the performance of individual tools.
The single hybrid modality MR / PET of the Siemens Biograph mMR.
Current regulatory status
|
Product name
|
Manufacturer
|
FDA
|
CE mark
|
|
Biograph™ mMR
|
Siemens S.p.A.
|
N.K103429 released on
2011-06-08
|
N.10433372 released on
2011-
05-24
|
|
Ingenuity TF PET-MR
|
Philips S.p.A.
|
yes
|
N.2251362 released on
2010-12-22
|
|
Tri-modality PET-CT+MR
|
GE Healthcare
|
yes
|
yes
|
Context
of use analysis
Currently the technology is used in hospitals
and advanced research centers where clinical research is accompanied by the
development of the technology itself.
GE's technology is installed in:
1. “University Hospital” - Zurich;
2.“University Hospital” - Korea and it's in
progress in:
other five sistems worldwide.
Siemens's technology is installed in:
1.IMP Erlangen;
2.Klinikum
rechts der Isar – Munich;
3.University
Hospital – Tubingen;
4.University
Hospital – Leipzig;
5.CEMODI –
Bremen;
6.University
Hospital – Essen;
7.MGH –
Boston;
8.NIH –
Bethesda;
9.Washington University – St. Louis;
and it's in progress in:
University College London Hospitals;
SDN,
Naples;
DKFZ –
Heidelberg;
Rigshospitalet
– Copenhagen;
University
of Noth Carolina – Chapel Hill;
Mt. Sinai
Medical Center – New York;
Indiana
University – Indianapolis;
Lawson
Health Research Institute – London, Ontario;
PLA 301 –
Beijing;
Parkway Novena Hospital – Singapore; Biopolis/CIRC – Singapore.
Philips's technology is installed in:
1.Mt. Sinai – New York;
2.University
Hospital – Geneva;
3.FZD –
Dresden;
4.CNIC –
Madrid
5.Pusan
National University
– Korea
Comparators
Due to the absence of any clear target disease
it is impossible to define any comparator. Manufacturers propose the following
comparators: MRI (Philips), PET-CT (GE), MRI or PET or PET-CT (Siemens)
Effectiveness and
safety
Methods for
systematic review of evidence profile, diagnostic accuracy, effectiveness and
safety
Literature
search
Search strategy
The
following electronic databases have been searched:
- National Library of Medicine’s
Medline database (PubMed);
The key words used were related only to the
index test [(biograph AND mMR) OR (ingenuity AND PET) OR "PET-MR" OR
"PET-MRI" OR "PET-MR" OR "PET-MRI")]. Period
restriction: from January 2006 (date of the literature search update of a
previous HTA document (Cuerva Carvajal 2007) till present. Language
restrictions: documents in English, Italian, French, Spanish, Portuguese,
German. Reference lists of identified articles have been checked for additional
references.
Inclusion criteria
- Types of studies: systematic reviews
and primary studies assessing the feasibility, diagnostic accuracy,
effectiveness and safety of the index test. Among primary literature, we have
included only full report with any study design with the exception of case
reports and case series with less than 10 patients.
- Participants: any type of medical
condition. We have excluded studies considering phantoms, animals, healthy
people.
- Index test: We have assessed studies considering any hybrid PET-MRI system
integrating Positron Emission Tomography (PET) with Magnetic Resonance (MR)
imaging and enabling the delivery in a single test session of
anatomical-functional fusion imaging. We have included studies using any
radioactive tracer for PET. We have excluded studies analyzing fusion of images
obtained during different test sessions.
- Outcomes of interest: any kind of
outcomes reported in studies, subdividing them in the following three
subgroups: feasibility outcomes, diagnostic accuracy outcomes (sensitivity,
specificity, likelihood ratios, diagnostic odds ratios, ROC curves), clinical
effectiveness and safety outcomes (i.e. quality of life, adverse events, time
to recurrence, disease free survival, overall survival).
- Comparator: any kind of potential diagnostic imaging test used in the standard
practice.
- Reference standard (for diagnostic
accuracy studies): any reference
standard considered.
Study
selection
We have used Reference Manager software
(version 10) to manage the references. The selection of the studies to be
included have followed these steps:
1. exclusion on the basis of title and
abstract;
2. full text retrieving of the
potentially interesting studies;
3. reading of the selected articles and
application of the inclusion criteria.
Selection have be performed by two independent
reviewers. The results have been compared and differences discussed.
Differences in the selection have been resolved by mutual agreement.
Data
extraction
Data have been extracted related to study
design, study population, index test, reference standard, comparator, outcomes,
and pre-test probabilities. Data extraction from included studies have been
carried out using single study tables of evidence.
Methodological
quality assessment
The following criteria have been used for the
quality assessment of different study designs:
- Systematic reviews criteria drawn
from the AMSTAR checklist [Shea B, 2007];
- Diagnostic cross-sectional studies
criteria drawn from the QUADAS checklist [Whiting P, 2003];
- Randomized controlled trials
criteria suggested by the Cochrane Handbook [Higgins JPT, 2009];
- Case control studies and cohort
studies criteria drawn from the New Castle-Ottawa checklist.
The quality of evidence have been summarized by
disease and by outcome according to GRADE method when possible.
Analysis
and synthesis
Studies have been analyzed and synthesized using a tabulation
constructed on the basis of the data extraction form and classified according to the following descriptors: medical
disorder, study design, number of included patients, outcomes assessed. Studies
results have been reported only descriptively.
Interpretation of results
Interpretation of the
studies’ results have been carried out in terms of numerosity, quality and
consistency of results.
Results
From the 256 eligible references we analyzed in
full text 48 studies. After application of inclusion criteria 1 case series was
included (Boss 2010). We excluded 4 case reports (Garibotto 2011, Miese 2011,
Thorwarth 2011, Wissmeyer 2011) and 1 case series of 8 patients (Boss 2011).
The only study included (Boss 2010) analyzed
the feasibility of PET-MRI in a series of brain tumour patients (10 subjects).
There are no data about diagnostic accuracy or clinical effectiveness.
The safety aspects of the technology
should be further developed with specific studies of the effects of radiation
and electromagnetic fields on patients and operators.
Potential
benefits for patients
PET-MRI may be useful in early diagnosis of
cancers and degenerative diseases and also allow for better monitoring of the
patient's condition. However, at present, the technology is still experimental,
and no evidence of scientific evidence in support of these considerations.
Manufacters indicate the following potential
benefits:
1.educing exposure to radiation;
improving 2.pediatric imaging;
3.visualization of the tumors that existing systems do not allow to view; 4.reduction in the time of the
examinations; execution of a single test for both 5.MR and PET results; reduction
in the time of reporting; decreasing doses of the contrast medium.
Investments for the acquisition of PET/MRI are
substantial and related to the construction of suitable premises and
facilities. Although operating costs are substantial and relate to the
maintenance and specialist staff involved. The manufacturers usually provide
the technology framework of agreements and specific research projects,
investments.
Costs
Methods for
costs and impact
Technical and cost data are important to
forecast structural, organizational and economic impact of PETMR on the Italian
NHS. Moreover - due to the experimental phase of the technology - the
definition of present marketing status and worldwide clinical and research
utilization is important to programme and refine future processes on PET-MRI.
Two surveys were planned with the aim at
collecting and defining the above reported contextual issues. In the first
survey each of the three manufacturers were formally contacted by AGENAS on
behalf of RIHTA and underwent a structured interview on the technical,
organizational and cost issues of each specific PET/MR machines. An ad hoc
questionnaire – with close and open-ended answers - was devised and will sent
to each manufacturer before the meeting between manufacturers’ and RIHTA’s
representatives. Data from the interview were analysed and reported
qualitatively. The second survey aimed at collecting data on the worldwide
diffusion of PET/MR and the clinical and research activities at present. We
identified researchers in the field through a preliminary literature search. A
structured questionnaire was devised and sent by post to the researchers
identified as responsible of the PET/MR centers. The questionnaire gathered
information on two topic areas: information about routine clinical activity and
research activity using PET/MRI.
The costs of the technology depend on the
Manufacturers:
1. GE: The cost of the PET-MRI system (including
shuttle) varies from € 3.750.000,00 to € 4.250.000,00, depending on the system
CT-PET provided (number slice of the TAC) and the MRI system (1.5T or 3T).
Maintenance cost by year is about 10% of the cost of the entire system (PETCT,
MRI and Shuttle).
2. Philips: The cost of the PET/MR system is
about €4.000.000,00. Maintenance cost by year is about 8% of the cost of the
system.
3. Siemens: The cost of a PET-MR Siemens is
around € 5.000.000,00. Maintenance cost by year amounts to € 300,000.00.
Potential
structural and organizational impact:
STRUCTURAL IMPACT
The structural impact of the new technology is
very important. The complexity of technology is linked to the management and
technical issues generated from the magnetic field, which require huge
resources related to the costs of technology investment, structural and
operational. The PET-MRI systems must be housed in specially designed and built
for this technology as well as provide suitable locations for the safety of
staff and patients.
The installation of a PET-MRI system requires
standard equipment and construction works for individual PET and MRI systems:
Faraday cage, leaded and magnetic shielding.
ORGANIZATIONAL IMPACT
Because of the current use of PET-MRI is mainly
experimental we have to consider the involvement of new and highly qualified
professionals (researchers, physical and engineers).
Conclusions:
Due to the lack of any evidence on the
diagnostic accuracy, clinical effectiveness and safety of PET-MRI for any kind
of patients we cannot recommend the PET-MRI for any clinical indication.
Further information about the fields of
application and the expected benefits by the application of the technology are
needed.
References:
1. Boss A, Bisdas S, Kolb A, Hofmann M, Ernemann
U, Claussen CD et al. Hybrid PET/MRI of intracranial masses: initial
experiences and comparison to PET/CT. J Nucl Med. 2010;51:1198-205.
2. Boss A, Stegger L, Bisdas S, Kolb A, Schwenzer N, Pfister M et al.
Feasibility of simultaneous PET/MR imaging in the head and upper neck area. Eur
Radiol. 2011;21:1439-46.
3. Cuerva Carvajal A, Villegas Portero R.
Tomografía por emisión de positrones combinada con resonancia magnética
(PET/RM). Positron Emisión Tomography combined with Magnetic Resonance
(PET/RM). Sevilla: Agencia de Evaluación de Tecnologías Sanitarias de Andalucía;
Madrid: Ministerio de Sanidad y Consumo, 2007.
4. Garibotto V, Vargas MI, Lovblad KO, Ratib O. A
PET-MRI case of corticocerebellar diaschisis after stroke. Clin Nucl Med.
2011;36:821-25.
5. Miese F, Scherer A, Ostendorf B, Heinzel A,
Lanzman RS, Kropil P et al. Hybrid (18)F-FDG PET-MRI of the hand in rheumatoid
arthritis: initial results. Clin Rheumatol. 2011;30:1247-50.
6. Thorwarth D, Henke G, Muller AC, Reimold M,
Beyer T, Boss A et al. Simultaneous 68Ga-DOTATOCPET/MRI for IMRT treatment
planning for meningioma: first experience. Int J Radiat Oncol Biol Phys.
2011;81:277-83.
7. Wissmeyer M, Heinzer S, Majno P, Buchegger F,
Zaidi H, Garibotto V et al. Y Time-of-flight PET/MR on a hybrid scanner
following liver radioembolisation (SIRT). Eur J Nucl Med Mol Imaging. 2011;38:1744-45.
