Magnetocardiography (MCG) is a technique used for measuring the magnetic field (MF) produced by the electrical activity of the heart. Unlike electrocardiography (ECG), which measures the electrical activity of the heart indirectly using electrodes placed on the skin, MCG is a contactless recording of the magnetic fields produced by the electrophysiological activity inside the heart using highly sensitive magnetic sensors placed outside the body. Another advantage of MCG is that the recording of cardiac MF is not significantly affected by the different conductivity and electrical resistance of the various tissues interposed between the cardiac source and the surface sensors.

As compared with ECG, a foundational research from the general theory of bioelectromagnetism describes the amount of potential additional information provided by MCG (1–7), stimulating bio-physicists to find ways to effectively measure cardiac MF. These attempts were finally achieved in the early 1960s, experimentally by recording the cardiac MF from an isolated rabbit heart preparation with a toroidal solenoid (8) and in humans by Baule and McFee (9), using two large magnetic sensor coils, although at the very low spatial resolution, which obviously made it still inadequate for any practical use, especially looking for MCG as a potential diagnostic tool in the clinical setting. Moreover, a major limiting factor was that the cardiac magnetic field's strength is very weak (in the range of 10⁻¹² to 10⁻¹⁵ T) compared with the Earth's MF (in the order of magnitude of 10⁻⁶ T); thus, MCG signals were strongly affected by environmental noise and practically useless compared with much easier recordable ECG. Baule and McFee tried to address this problem, using the sensor coil prototype arranged in a sort of “gradiometer” configuration, needing anyway the recording to happen in a “quiet” ideal location far from any potential magnetic interference.

Providing a significant improvement in sensitivity and spatial resolution of MF measurements, a major milestone in MCG was the invention of the first superconducting quantum interference device (SQUID) (10) and the installation of SQUID within the magnetically shielded room (MSR) of the Massachusetts Institute of Technology (MIT) that radically reduce external electromagnetic interference by at least a factor of about 1,000 (11, 12), finally providing an experimental setup and a magnetic signal-to-noise ratio (SNR) suitable for recording cardiac and even brain biomagnetic signals (13, 14). Since then, the research work of a few pioneers set the theoretical basis for cardiac MF interpretation and explored several potential applications of MCG as a reliable method to improve non-invasive diagnosis of cardiac abnormalities (1, 3, 15–21).

Although electromagnetic shielding (EMS) provided the best SNR, increasing the reliability and accuracy of MCG (22), highly efficient MSRs were very expensive, not easy to install everywhere, and especially not suitable in the clinical environment. Thus, aiming for clinical applications of magnetocardiography at scale, it became evident that cheaper and simpler alternatives were needed to dampen electromagnetic noise in clinical settings, which are well-known magnetically noisy environments.

To avoid the need for MSRs, the first technological alternative was the invention of superconducting pick-up coils designed as second- or higher-order gradiometers that would primarily measure the MF gradient closest to the source ignoring magnetic fields from further away (e.g., the environmental noise) (23). The efficacy of such a less expensive unshielded approach enhanced the opportunity to get more scientists involved in the field of biomagnetism research (24–32) and to attempt the first installation of a single-channel MCG system in a standard hospital unshielded room, testing and validating the potential use of MCG as a diagnostic tool “to the patient's bedside,” in a minimally adapted unshielded cardiology lab designed for simultaneous MCG and clinical interventional electrophysiological study (27, 33–35).

At that time, only single-channel devices were available, and the normal component of cardiac MF had to be sequentially measured at different locations in front of the chest, typically in a rectangular normalized (e.g., the “Finnish”) grid (24, 25). An alternative approach to single-channel mapping came from Stanford, where the three orthogonal components of cardiac MF (so-called vector magnetocardiography) were measured at a single position over the heart, based on the theoretical assumption that like in vector electrocardiography, the three-dimensional (3D) motion of the magnetic heart vector represents the overall activity of the heart (2, 36–38).

Another crucial step forward was the development of multichannel SQUID devices, allowing simultaneous multipoint mapping of the cardiac MF, which was absolutely needed for more reliable and precise real-time detection of its dynamic variation due to transient normal and/or abnormal electrophysiological events, such as acute myocardial ischemia or arrhythmias.

Since then, the history of magnetocardiography has become somehow complex and slowed down, with a progressive reduction of MCG scientific production presented at the biannual biomagnetism conferences, as low as less than 10 abstracts at the Biomag 2022 Conference in Birmingham (39). The alternating phases of clinicians’ skepticism and renewed enthusiasm (40) were often driven by the different perspectives among basic scientists, mostly favoring the development of huge and much more expensive installations in MSRs to guarantee optimal sensitivity and 24/7 reliability of MCG measurements but “de facto” far from clinicians’ needs seeking for a new diagnostic tool to the patient's bedside instead. Indeed, since the 1980s, multichannel installation in highly performant MSRs was the most preferred choice also for MCG, under the influence of faster-growing research and development for clinical applications of magnetoencephalography (MEG) (26, 41), which diverged major investments in that direction. In fact, although MEG feasibility required heavy and expensive EMS, its development was favored by the tremendous impact that neuromagnetism provided for the non-invasive functional imaging of brain electrophysiology compared with the huge limitation of the electric counterpart available at that time (42–46). Consequently, only a few centers of excellence working with innovative shielded multi-SQUID systems, mainly driven by bio-physicists and somewhere in time-sharing with neurology, continued basic MCG research (44–47) and several studies of clinical interest in collaboration with cardiology departments (48–65).

On the other hand, most clinicians were skeptical and considered unnecessary the sophisticated and expensive MCG technology, given the ready availability of more affordable, and overall well-established diagnostic tools (although mostly invasive) for cardiac clinical electrophysiology. Only a small group of “MCG believers” envisioning the yet unleashed innovative diagnostic power of this technology (if made available to the patient's bedside) devoted their main research focus to the development and validation of less expensive and more scalable multichannel MCG mapping systems, reliably operated in unshielded hospital environments (66–78). This pioneering vision of MCG mapping as a unique novel method for non-invasive 3D electroanatomical imaging (EAI) and localization of cardiac electrophysiological mechanisms with its potential to guide “aimed” myocardial biopsy and interventional transcatheter treatment of arrhythmogenic substrates prompted the development of a novel and easy-to-use unshielded MCG multichannel prototype reliable even in catheterization laboratories where noisy radiological and interventional equipment were necessary (79).

The parallel research efforts carried out with shielded and unshielded MCG over the last three decades have enlarged the knowledge about the pros and cons of these two approaches and provided evidence of well-defined fields of clinical application, such as the emergency triage of patients with chest pain, the diagnosis of different kinds of ischemic and non-ischemic cardiomyopathies, the heart transplant rejection (80, 81), the non-invasive 3D EAI of arrhythmogenic substrates and mechanisms (82), fetal MCG, and in particular the prenatal diagnosis of arrhythmogenic risk and cardiomyopathies (54, 83). Moreover, MCG has proven useful for the non-invasive study of experimental intact animals (84) and contactless high-resolution investigation of experimental electrophysiology of isolated heart (85) and cardiac tissue models (86).

Aside from a large body of relevant research and meta-analysis papers, there are also several comprehensive reviews, Biomag Conference Proceedings, and book chapters summarizing the history and the results of decades of experimental and clinical MCG research, as well as the major technological advancements obtained with shielded and unshielded settings (44–46, 82, 87–105).

Since the late 1970s, our group worked to bring MCG to the patient's bedside and to use it as a diagnostic tool in unshielded hospital environments (27, 33). Thus, we will focus on providing a review of the most relevant steps of MCG starting from our experience in developing devices and protocols for experimental and clinical validation of unshielded MCG as an unrivaled method for contactless non-invasive cardiac functional electrophysiological imaging, discussing such achievements in the light of gold standard MCG measurements carried out in MSRs in collaboration with other biomagnetism centers of excellence. Finally, we will also provide our personal vision of the future of MCG in light of present and foreseen improvements in magnetic sensor technology, innovative methods for signal processing, and less expensive active shielding approaches.

Indeed, MCG was born unshielded (8, 9, 15, 21). With the exception of the MIT (106–108), most MCG research in the early 1970s was attempted in very low-noise rural laboratories, wooden cottages, or underground locations, using first-, second- or higher-order gradiometers as pick-up coils, investigating healthy subjects and pregnancy as well as patients with cardiac disorders (6, 24, 25, 27, 29, 109–114). Although more susceptible to external electromagnetic interference and somehow less sensitive, unshielded MCG devices had the advantage of being less expensive and theoretically portable to the patient's bedside. Such potential was originally tested at the Catholic University Hospital of Rome in January 1980 by bringing the single-channel MCG prototype, designed and built by the researchers of the Italian National Research Council's Institute for Solid State Electronics (CNR—Consiglio Nazionale delle Ricerche—Istituto di Elettronica dello Stato Solido), in a standard hospital room of the Policlinico Gemelli and providing the first demonstration that its sensitivity was good enough to record beat-to-beat MCG in an unshielded clinical environment (Figure 1).

The CNR's prototype was later replaced by an industrialized single-channel system in 1982 (Elettronica SpA, Rome) (Figure 2A). With that system and new software tools for digital data acquisition and signal averaging, it was possible to detect even the ultra-weak magnetic fields generated during the ECG PR interval to attempt non-invasive MCG detection of the His bundle signal (115). Although a preliminary magnetic measurement of the PR interval's MF had been reported in 1978 (116), high-resolution (HR) MCG recordings of the PR segment were carried out independently both with unshielded MCG and in MSR since the early 1980s (27, 33, 117, 118). The physiological interpretation of HR MCG waveforms of the PR interval was controversial (34, 119–122) until the nature of the so-called “ramp-like” pattern recorded during the PR interval (Figure 3A) was definitely clarified within the development of software for automatic MF mapping and interactive subtraction. In fact, by subtracting the atrial repolarization field component from the whole PR interval's MF, a weaker remaining MF generated by sources moving from the AV junction downward along the interventricular septum was identified, consistent with the activation of the His–Purkinje System (123), coherently with the output of a more advanced mathematical model of the normal AV conduction pathways (124–126) and later by simultaneous MCG and invasive His bundle electrogram recording (127) and by direct comparison of atrial magnetic repolarization field distribution and simultaneous atrial monophasic action potential recording (128) (Figure 3B). Further results on MCG recording of His bundle activity were subsequently reported also by other studies conducted in MSRs (129–131).

While clinical studies, which was carried out in specialized centers with shielded and unshielded SQUID-based MCG systems, enhanced the evidence for MCG 3D electroanatomical localization accuracy and for risk assessment of arrhythmogenic mechanisms/substrates (82, 83, 90, 226, 245–251), a renewed interest for biomagnetic sensor technology has raised again not only at the academic but also at the industrial level (252, 253). In fact, apart from the traditionally available multichannel cryogenic MCG systems working in MSRs (246, 254–259) and a more downscaled price for sequential unshielded MCG mapping (77, 256–259), three younger companies have manufactured innovative multichannel MCG devices, based on different sensor technologies, all of them specifically designed for clinical application at minimized running costs and with optimized operational simplicity. All of them have gathered regulatory clearance for the recording of human cardiac magnetic fields. Two operate in unshielded environments, while the third one still needs performant EMS, based on optical magnetometry.

Magnetocardiography and in particular unshielded MCG are celebrating its 60th birthday, but is not yet a widely diffused and well-accepted clinical tool, although theory and experimental research suggest and confirm that it can provide additional diagnostic information not achievable with electrocardiography alone (1, 2, 4–6, 9, 16, 107).

Indeed, a large body of literature has provided evidence that MCG enhances the non-invasive diagnostic and prognostic capability in numerous clinical fields, such as but not limited to the earlier detection of (sometimes electrically silent) myocardial ischemia (59, 88, 90, 323, 319), the preventive arrhythmogenic risk assessment in adults (53, 225, 325–322) as well as in fetuses (83, 323, 324), and the diagnosis of inflammatory cardiomyopathy (40, 87, 218, 325) and of microvascular diseases (96, 326).

The usefulness of MCG for a better understanding of the arrhythmogenic mechanisms underlying the high-risk J syndromes (225, 327–336); the identification of atrial arrhythmogenic vulnerability (248), of left atrial dysfunction (330), and of the atrial propagation pathways (228); and the dominant frequencies (181, 183, 189, 232) in patients with atrial fibrillation, as well as providing accurate pre-interventional 3D localization of arrhythmogenic substrates (128, 193, 247, 249, 331), has been widely reported. However, the lack of a clinical breakthrough at scale is evident.

Trying to identify the possible reasons for such translational difficulty, already in 2005, we had suggested two major causes that (1) MCG technology was at that time still too sophisticated, expensive, and not available to the patient's bedside and (2) a sort of vicious circle, where the unavailability of MCG devices easily applicable to the clinical setting with the lack of a widespread knowledge and understanding of its potential, and some uncertainty on the results from clinical trial addressing some specific indications, enhanced the skepticism of both clinicians and investors with consequent persistent lack of sufficient resources to accelerate the research and development of novel and scalable clinical devices.

The “chimera” to solve the problem with highly reliable large-scale MCG systems providing the best signal quality in MSRs was predominant but contrasted with the “paradox” of trying to introduce new huge, highly expensive, and relatively complex-to-operate experimental technologies within the established electrocardiology world, where numerous standard solutions were already available. For decades, we had suggested and pursued a vision centered on the development of reliable, budget-priced, portable, and preferentially non-cryogenic, user-friendly devices for multimodal cardiomagnetic imaging, with software tools to simplify data fusion with other imaging techniques, as probably the most reasonable and effective solution to favor the diffusion of MCG at scale (102). However, the times and technology were not ready, in spite of evidence that, with appropriate adaptive solutions, multichannel MCG was feasible and reliable even in a clinical laboratory fully equipped for interventional cardiac electrophysiology (67).

Nowadays, the historical (and sometime hysterical) “to shield or not to shield” debate is going to become obsolete. In fact, from one side, improved shielding technologies provide flexible solutions, more easily adaptable to clinical environments and specific needs, at affordable costs. On the other hand, the new miniaturized non-cryogenic OPMs featuring a sensitivity comparable to the SQUID sensors aimed to be wearable for cardiomagnetism and neuromagnetism. Thus, using sensors which still need a MSR (e.g., the zero-field OPMs and the MR sensors), even those MCG devices could be used in time-sharing with MEG, within the same downscaled MSR, with sensitive reduction of the relative costs. Obviously, high-performance EMS still remains the preferred choice when the highest possible high resolution is needed, especially for experimental research.

Instead, as concerns most routine clinical MCG applications, there is an increasing evidence that progress in magnetic sensor technology combined with more advanced signal denoising methods is rapidly reaching the requirements for the near-future availability of several novel device variants for budget-price unshielded MCG, covering the needs of different deployment scenarios, from ED triage for suspected ACS (87, 259) to large-scale screenings of ambulatory patients (189) and to contactless monitoring during interventional cardiology (128) or badly burned patients and even foreseen for dynamic long-term assessment of cardiac MF dynamics (285).

The concept was clearly demonstrated by the excellent work by the Indira Gandhi Centre for Atomic Research's (IGCAR) researchers who, after EEMD processing, obtained a similar MCG signal quality with their DC-SQUID-based first gradiometer inside and outside the MSR (314); thus, we could anticipate that a similar result could at least be obtained with the most recent high-sensitivity scalar OPMs (279, 280, 282, 323, 319) and perhaps in the future even with zero-field SERF OPM gradiometers (325). However, since almost all those new OPMs were originally developed for MEG, their sensitivity and accuracy for deeper cardiac source localization need to be evaluated. Experimental use of much cheaper sensor would reduce the development and retailed costs of future devices for unshielded multichannel MCG. However, depending on technology, some of them still need EMS or at the moment have less sensitivity compared with SQUID and OPMs. Aside from hardware development, another limitation for MCG clinical adoption is the relative lack of software for MCG 3D EAI, at least non-inferior to that provided by recent ECGi. In fact, after its first appearance as a clinical tool (242), advanced software for ECGi and its integration with invasive 3D EAI has rapidly become available and is nowadays currently used for non-invasive study of arrhythmogenic electrophysiological mechanism and pre-interventional localization study of target substrates (243, 244, 320, 321), despite some pitfalls found in validation studies with the isolated and perfused pig heart model (322) and by comparison with invasive contact mapping (323). Might MCG 3D EAI be more competitive? For 3D localization accuracy of the arrhythmogenic site of origin, surely yes (181, 246, 247, 249). However, dedicated software packages for MCG endocardial and epicardial activation imaging and automatic integration with invasive 3D EAI are still lacking. With more adequate software tools, the advantages of 3D EAI based on unshielded MCG would be the speed and comfort of contactless mapping, to be inexpensive (no need of consumables, if performed with non-cryogenic devices) and better patient acceptance.

The development of wearable MCG devices may apparently seem in contrast with the MCG benefit of being a contactless method for easier and more comfortable cardiac mapping. Indeed, although a wearable device could theoretically favor a more realistic evaluation of cardiac MF dynamics (285), movement artifacts could markedly affect the reliability of such kind of measurements. However, an appropriately designed wearable mapping system (250) could be highly useful to improve MCG sensitivity and localization accuracy of weaker and deeper cardiac sources independently from their orientation, thus avoiding the need for simultaneous BSPM or favoring optimal integration of the two mapping methods for more accurate 3D/4D EAI (324).

Although the primary endpoints of the majority of MCG clinical trials have mostly focused on the demonstration of higher predictive accuracy of the method to diagnose or exclude ischemic heart disease (87, 88), at any possible stage from acute coronary syndromes to microvessel dysfunction, in this review, we have tried to summarize several relevant points demonstrating that the value of the information provided by cardiac MF recordings extends much beyond that clinical target. In fact, when the ECG and cardiac enzyme patterns cannot yet be diagnostic, the higher sensitivity of MCG in detecting myocardial ischemia at an early stage is only one of the advantages arising by the more comprehensive biomagnetic electrophysiological assessment, which has the potential to non-invasively detect electrogenic phenomena at cellular and even subcellular levels (86, 208). Moreover, as experimentally demonstrated by Cohen with DC-MCG measurements, it is possible to detect an ischemia-related diastolic injury current (106). Such “silent” abnormal electrotonic current flowing may usually arise at the border zone of an ischemic zone and can be arrhythmogenic if reaching the excitability threshold of the surrounding normal tissue (166). Unfortunately, although requiring EMS, DC-MCG is also clinically feasible (107) and with appropriate 3D electroanatomical integration with the structural and functional imaging provided by cardiac MR delayed enhancement imaging, it could be theoretically possible to detect and localize a potentially lethal injury current before it reaches the strength to generate a sustained VT/VF and sudden death in post-MI patients or in other kinds of advanced cardiomyopathies with extended pathological anisotropy.

Another example of unexplored potential information of MCG is suggested by a seminal experimental study of Benjamin Scherlag (the father of the method for clinical recording of the His bundle electrogram), who demonstrated that graded low-level EMFs applied to either the left or the right vagosympathetic trunks alter the sinus heart rate, the AV conduction, and the heart rhythm, facilitating the pacing inducibility of atrial fibrillation, in a canine model (325). Similar effects were observed when the EMF was applied with two larger Helmuth coils surrounding the whole chest and focused on the dog's heart. Interestingly, in a subsequent study, the same authors found that a pulsed EMF applied to the vagal trunks, or non-invasively across the dog's chest, can significantly reverse AF inducibility by inhibiting the neural activity of the atrial ganglionated plexus (326). Another elegant research has shown that non-invasive low-frequency electromagnetic stimulation of the left stellate ganglion (LSG) also reduces the occurrence of ventricular arrhythmia induced by acute myocardial infarction in a canine model (327). How this research connects to MCG? Indeed, it does. In fact, as pointed out by Wang et al., although many mechanisms, which might provide the basis for how the animals detect magnetic fields, have been proposed., the mode of transduction for the magnetic sense remains unknown. Following the same biomagnetic approach to study with MEG the effect of transcranial magnetic stimulation, MCG could be the right tool to explore and understand how noninvasive electromagnetic stimulation of cardiac autonomic innervation may affect cardiac electrophysiology, with proarrhythmic or antiarrhythmic effects (327).

Finally, since it is nowadays well known that the heart has its own “little brain” (328) and that the “heart-to-brain” afferences are at least functionally relevant as the “brain-to-heart” efferences, it can be hypothesized that the cardiac MF could be a third independent wireless “heart-to-brain” communication pathway, as preliminarily advanced by the HeartMath Institute's research (329). Simultaneous MCG and MEG mapping recording could shed some new light about the real possibility of contactless heart–brain synchronization. Practically impossible until now for the limitation related to the dimension and costs of cryogenic instrumentations, such research could become soon feasible with the novel OPM-based wearable MEG and MCG devices and in the near future even in unshielded environments (277, 279–281, 285, 336, 330).

Roth has concluded his interesting review of the first 60 years of biomagnetism by stating that it “remains a growing and developing field of study,” and wishing that “the next sixty years of biomagnetism might well be more momentous than the first sixty” (331).

As concerns the future of MCG, we are somehow more optimistic, because, as summarized here, decades of research have demonstrated that unshielded MCG is feasible and reliable providing the same information of clinical interest obtained with more expensive and bulky MCG systems working in MSR. Therefore, we feel confident that MCG is ready to reach its clinical breakthrough very soon.

Surely the future of MCG will continue in double parallel rails, shielded and unshielded, depending on local needs and finalities. However, whereas heavy EMS will remain a prerogative of highly specialized research centers, we definitely believe that only the development of reliable user-friendly unshielded devices will favor the widespread acceptance of MCG at the clinical level. Luckily, after many years of stagnation, present acceleration of sensor technology, and implementation of more efficient active shielding combined with AI-based signal denoising methods, we foresee that a larger choice of budget-price instrumentations for unshielded MCG mapping will be available in a relatively short time, allowing the diffusion of such novel medical devices at scale in hospitals and their clinical validation in the real world, initially as a routine add-on to standardized electrocardiography, but soon as a more rapid and efficient method for more comprehensive non-invasive electrophysiological evaluation, especially in centers where the high number of patients is to be screened. In fact, it takes less time for a standard 90-s (or even 5-min) MCG mapping than to perform a standard 12-lead ECG, especially in older patients with limited mobility.

As concerns the presently available new systems under the clinical testing, SQUID sensors are still the reference gold standard with the best sensitivity in unshielded environments; thus, a standalone novel multichannel vector mapping instrumentations (e.g., Figure 7A) with an efficient permanent cooling to get rid of liquid helium consumption may represent an intelligent more advanced cost-effective solution for multipurpose clinical applications of unshielded clinical MCG, including real-time 3D magnetic mapping and imaging during stress/pharmacological tests (225, 332–334), minimally invasive interventional procedures (128), and fetal MCG (185).

On the other hand, for large-scale routine ambulatory applications and to bring MCG to the patient's bedside, more compact movable devices fully reliable in unshielded hospital rooms are necessary (e.g., Figure 7B), obviously based on non-cryogenic sensor technologies, whose cost however might widely differ, depending on the type of sensors chosen as the front end.

Downscaled MSRs may be an alternative to profit of the higher sensitivity of zero-field OPMs even in noisy hospital environments (e.g., Figure 7C), if one accepts the limitations of partial visual control of the patients during data acquisition, the need for a wide space, and the problem of claustrophobia.

Apart from hardware developments, for clinical applications, looking at MCG as a powerful method for contactless and radiation-free 3D and potentially 4D functional imaging of cardiac electrophysiology (335), the development of more advanced software tools to merge MCG information in real time with other non-fluoroscopic (and/or nuclear medicine) imaging techniques (e.g., MRI and/or echocardiography (336) is absolutely a primary target to focus on. Multimodal 4D integration of magnetic current density imaging could become an unrivaled method to non-invasively investigate the dynamics of arrhythmogenic mechanisms occurring into the abnormal substrates due to ischemic and non-ischemic cardiomyopathies (including some channelopathies) (337). This would obviously allow more precise pre-interventional planning of the best interventional approach (e.g., endocardial vs. epicardial) for catheter ablation or for CRT or CCM treatments.

Last but not least, the standardization of MCG data acquisition, postprocessing, and analytic methods is required, providing shared and validated diagnostic criteria, independently of the hardware technology used in different devices. A tentative standardization of MCG was already defined by an “ad hoc committee” many years ago, during the NATO Conference on Biomagnetism (43) and the Fourth International Conference on Biomagnetism (338), held in Rome in 1982. However, even simple recommendations [e.g., the color code for MF interpretation, as specified in Figure 2, or the software tools to convert MCG data to a common format (339)], remained essentially unfollowed along decades of research, so that the results of MCG studies (and of clinical trials) so far carried out are only partially comparable and even less sharable in a common database.

Magnetocardiography is a multipurpose tool for contactless non-invasive functional imaging of cardiac electrophysiology, providing additional diagnostic information and more comprehensive electroanatomical imaging compared with electrocardiographic methods only. However, after more than 50 years of experimental and clinical research, MCG has not yet been accepted as a diagnostic method at scale.

In this review, relevant MCG milestones, achieved with cryogenic and non-cryogenic magnetic sensors operating in shielded and unshielded experimental and clinical setups, have been referenced and compared. Possible reasons for the still missing acceptability in the real clinical world have been discussed, based on over four decades of personal experience.

The unshielded approach has proven reliable to provide information of diagnostic interest equivalent to those obtained with more demanding systems needing heavy electromagnetic shielding. This suggests that the availability of next-generation unshielded devices will finally bring MCG to the patient's bedside, favoring its clinical application at scale.

The ongoing progress in magnetic sensors, active shielding, and denoising technology let us foresee the development of innovative solutions enhancing the reliability of unshielded MCG and the possibility to produce reliable and portable instrumentations, better tailored for specific clinical applications through optimal integration with other non-invasive imaging techniques and with electrocardiographic recordings when appropriate.

Finally, although the lack of standardization and the wide variability of MCG instrumentations, local experimental and clinical setups, and investigational protocols has made it difficult so far, a joint effort to centralize all potentially available MCG “big data,” converted into a common format with appropriate digital tools [e.g., (339)], could provide a valuable sharable database for wide retrospective studies demonstrating the real diagnostic potential of MCG based on statistically robust analyses. Such information would be extremely important to guide the development of novel MCG medical devices and the design of future more coordinated prospective multicenter clinical studies.