Sodium (23Na)-Imaging As Therapy Monitoring in Oncology – Future

Clinical Oncology Sodium (23Na)-Imaging as Therapy Monitoring in Oncology – Future Prospects Stefan Haneder, M.D.1; Stefan O. Schoenberg, M.D.1; Simon Konstandin, Ph.D.2; Lothar R. Schad, Ph.D.2 1 Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany 2 Computer-Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany Introduction “Form follows function” – tumor regression. Consequently, the ology benchmark of functional MR Louis Sullivan, 1896 RECIST Working Group addressed this sequences seems to be nuclear medicine Whilst this concept was originally applied point in the context of the new approaches, already fixed in guidelines to modern architecture, it could well RECIST1.1 criteria [1]: as PERCIST 1.0 [2]. Second, further multi- become a highly appropriate maxim for „A key question considered by the center, international studies are required future imaging and therapy concepts. RECIST Working Group in developing to obtain reliable data for (functional) Magnetic resonance imaging (MRI) has RECIST 1.1 was whether it was appropri- MR approaches. Third – not explicitly, but continually developed into a powerful, ate to move from anatomic unidimen- indirectly – the radiology community widely used diagnostic tool and offers sional assessment of tumour burden to should not abandon the assessment of the opportunity to expand traditional either volumetric anatomical assessment new functional approaches and should imaging concepts based on morphologi- or to functional assessment with PET try to implement them in clinical set- cal information. In the future, the pure or MRI. It was concluded that, at present, tings. The arsenal of current functional morphology will remain a central com- there is not sufficient standardisation or MR imaging approaches includes diffu- ponent of multimodal imaging, but will evidence to abandon anatomical assess- sion-weighted imaging (DWI), diffusion be flanked increasingly by functional ment of tumour burden. The only excep- tensor imaging (DTI), arterial spin label- approaches reaching far beyond the cur- tion to this is in the use of FDG-PET ing (ASL), blood-oxygenation level depen- rent imaging standards. In oncological imaging as an adjunct to determination dent imaging (BOLD) and sodium (23Na)- therapy follow-up the drawback of of progression. [...]“ imaging. DWI [3] should be emphasized relying on pure morphology is widely This statement contains several basic as a kind of paradigm shifting technique. known, resulting, for example, from implications for future MR strategies of Since the 1990s DWI has been performed delayed morphological reflection of therapy control. First, the internal radi- for intracranial diseases and has contrib- 1A 1B 1 Sequence design for 3D radial RF ky acquisition with global excitation. Ab- solute gradient values data acquisition are shown for standard radial acquisi- t tion with constant gradient readout (|G|Radial) and sampling density- weighted apodization (|G|SDWA) for intrinsic filtering. Due to hardware k |G|Radial x restrictions the gradient adaption begins at t = t0 with gradient ampli- 1C tude G . The echo time TE is defined t0 0 as the time interval between the mid- dle of the RF pulse and the beginning G0 |G|SDWA of data acquisition with readout dura- tion TRO. The k-space sample points are exemplarily shown in the kxy-plane TE TRO for standard radial (1B) and SDWA (1C) acquisition. Figure adapted from [18]. 72 MAGNETOM Flash · 2/2013 · www.siemens.com/magnetom-world Oncology Clinical uted to the detection of early stroke. k-space homogeneously yielding higher formal radiotherapy in a long-term fol- But in recent years the number of studies SNR: twisted projection imaging (TPI) low-up in patients after gastric cancer has increased substantially, evaluating [14], 3D cones [15], density-adapted [37], has been shown. In musculoskele- this method in detection and character- projection reconstruction [16, 17]. Since tal imaging, for example, different carti- ization of lesions, especially in the field filtering is usually applied to sodium lage repair approaches in the knee were of oncology and the possibility of (early) images as a post-processing step, sam- evaluated with 23Na-MRI at 7T [38-40] tumor treatment response [4-8]. This pling density-weighted apodization and presented marked differences in remarkable success story cannot (yet) be (SDWA) with intrinsic filtering [18, 19] comparison to native cartilage. applied to 23Na imaging, but we are is preferred when using short readout Increased sodium concentrations were witnessing continuous development. durations (Fig. 1). Anisotropic 3D imag- found in different brain tumors relative ing sequences using cones [20] or to normal brain structures [41, 42]. An Physiological and technical basics twisted projection imaging [21] were up to threefold increase in TSC can be 23Na ions play a fundamental role in recently developed for applications observed in human stroke [43] allowing human life and can be traced – similar where anisotropic resolutions are monitoring of the progression of stroke to protons (1H) – ubiquitary in the human needed (e.g., cartilage). pathophysiology [44, 45]. Surprising body. Fluxes of 23Na ions in cells and The technical developments of acquisi- results revealed a study about relapsing- across cell membranes are central part tion strategies and sequence design over remitting multiple sclerosis at early of many processes of cell activity. Up to the last decade were accompanied by and advanced stage. TSC was increased 70% of the energy from adenosine tri- MR hardware improvements. The trend inside demyelinating lesions in both phosphate (ATP) hydrolysis is used for to higher field strengths and stronger groups of patients, but TSC accumula- the Na+-K+-ATPase, which pumps three gradient systems was continued and led tion dramatically increases in the Na+ ions out of the cell while two K+ ions not only to a routine use of 3T MR scan- advanced stage, especially in the nor- vice versa [9]. An extracellular concen- ners in patient care but to a growing mal-appearing brain tissues, concomi- tration of ≈145 mM and an intracellular number of 7T whole-body-MR installa- tant with disability [46]. Furthermore, concentration of ≈12–20 mM (10) are tions worldwide. The electro-physiologi- 23Na-MRI provides a non-invasive solu- maintained in healthy tissue by this cal characteristics of 23Na predestine tion to distinguish viable from nonviable pump mechanism, which leads to a the implementation of higher field myocardial tissue after myocardial mean tissue sodium concentration (TSC) strengths. Complementary progression infarction in an animal model [47] and of about 50 mM. Pathologic changes can be stated for coil design. Meanwhile in humans [48, 49]. TSC measurements such as tissue injury, edema, or necrosis multi-channel 23Na coils are commer- have shown an increased signal mainly result in a degradation of Na+-K+-ATPase cially available and experimental new in nonviable myocardium after infarction and hence in an increase in TSC from designs – as a double-tuned two-port due to loss of cell membrane integrity. 50 mM up to 145 mM in case of cell surface resonator for 23Na- and 1H-imag- Despite the never-ending discussion of burst [11]. ing [22, 23] – have been introduced. necessity of separating intra- and extra- From an electro-physiological point-of- cellular 23Na components, TSC offers a view, some physical characteristics of Oncologic therapy monitoring using unique tool for measuring tissue viability 23Na hamper the simple application for 23Na MRI – quo vadis? noninvasively. The pathophysiology phe- MR imaging. The sodium nucleus has Taking into account the above-described nomena in almost all acute pathologies a spin of 3/2 and is therefore subject to technical developments over the last (stroke, myocardial infarction) are mainly quadrupolar relaxation resulting in a few years, a kind of renaissance of 23Na- based on the idea of changing 23Na envi- biexponential T2 decay with relaxation MRI and the determination of tissue ronments e.g. due to the loss of cell times of T2f* 0.5-8 ms and T2s* sodium content (TSC) can be stated. membrane integrity and the following 15–30 ms for the fast and slow compo- Feasibility of 23Na-MRI for in vivo imag- adjustment of intra- and extracellular nent, respectively [12]. Additionally, ing of physiological conditions has been 23Na concentrations. Laymon et al. [50] sodium MRI suffers from low in vivo con- demonstrated in various parts of the described that cell membrane depolar- centration with a weak gyromagnetic human body, e.g. kidney [24-26], carti- ization preceding the large degree of cell ratio of only ¼ of that for 1H resulting in lage and musculoskeletal in general [12, division in neoplastic tissue leads to an an approximately 10-fold lower MR sen- 27-29], brain [30, 31] heart [32-34] and increase in the intracellular sodium con- sitivity compared to 1H MRI with about prostate [35]. Initial translation from centration (ISC) and a concomitant rise in 10,000-fold less signal. Consequently, physiology to pathophysiology was cor- the total TSC. In human brain tumors, signal-to-noise ratio (SNR)-efficient respondingly addressed in a broad spec- Ouwerkerk and co-workers showed that acquisition strategies with short echo trum of organs and different pathologies. measured 23Na changes within the tumors times such as the radial scheme [13] The possibility of imaging of trans-

Load more