Superficial white matter (SWM) contains the most cortico-cortical white matter connections in the human brain encompassing the short U-shaped association fibers. Despite its importance for brain connectivity, very little is known about SWM in humans, mainly due to the lack of noninvasive imaging methods. Here, we lay the groundwork for systematic in vivo SWM mapping using ultrahigh resolution 7 T magnetic resonance imaging. Using biophysical modeling informed by quantitative ion beam microscopy on postmortem brain tissue, we demonstrate that MR contrast in SWM is driven by iron and can be linked to the microscopic iron distribution. Higher SWM iron concentrations were observed in U-fiber–rich frontal, temporal, and parietal areas, potentially reflecting high fiber density or late myelination in these areas. Our SWM mapping approach provides the foundation for systematic studies of interindividual differences, plasticity, and pathologies of this crucial structure for cortico-cortical connectivity in humans.

Iron is essential for neurons and glial cells, playing key roles in neurotransmitter synthesis, energy production and myelination. In contrast, high concentrations of free iron can be detrimental and contribute to neurodegeneration, through promotion of oxidative stress. Particularly in Parkinson’s disease (PD) changes in iron concentrations in the substantia nigra (SN) was suggested to play a key role in degeneration of dopaminergic neurons in nigrosome 1. However, the cellular iron pathways and the mechanisms of the pathogenic role of iron in PD are not well understood, mainly due to the lack of quantitative analytical techniques for iron quantification with subcellular resolution. Here, we quantified cellular iron concentrations and subcellular iron distributions in dopaminergic neurons and different types of glial cells in the SN both in brains of PD patients and in non-neurodegenerative control brains (Co). To this end, we combined spatially resolved quantitative element mapping using micro particle induced X-ray emission (µPIXE) with nickel-enhanced immunocytochemical detection of cell type-specific antigens allowing to allocate element-related signals to specific cell types. Distinct patterns of iron accumulation were observed across different cell populations. In the control (Co) SNc, oligodendroglial and astroglial cells hold the highest cellular iron concentration whereas in PD, the iron concentration was increased in most cell types in the substantia nigra except for astroglial cells and ferritin-positive oligodendroglial cells. While iron levels in astroglial cells remain unchanged, ferritin in oligodendroglial cells seems to be depleted by almost half in PD. The highest cellular iron levels in neurons were located in the cytoplasm, which might increase the source of non-chelated Fe3+, implicating a critical increase in the labile iron pool. Indeed, neuromelanin is characterised by a significantly higher loading of iron including most probable the occupancy of low-affinity iron binding sites. Quantitative trace element analysis is essential to characterise iron in oxidative processes in PD. The quantification of iron provides deeper insights into changes of cellular iron levels in PD and may contribute to the research in iron-chelating disease-modifying drugs.

We demonstrate a technique for precision sensing of temperature or the magnetic field by simultaneously driving two hyperfine transitions involving distinct electronic states of the nitrogen-vacancy center in diamond. Frequency modulation of both driving fields is used with either the same or opposite phase, resulting in the immunity to fluctuations in either the magnetic field or the temperature, respectively. In this way, a sensitivity of 1.4 nT Hz −1/2 or 430 µK Hz −1/2 is demonstrated. The presented technique only requires a single frequency demodulator and enables the use of phase-sensitive camera imaging sensors. A simple extension of the method utilizing two demodulators allows for simultaneous, independent, and high-bandwidth monitoring of both the magnetic field and temperature.Negatively-charged nitrogen-vacancy (NV) color centers 1,2 have become a popular tool for precision magnetic-field sensing at the nano-to milli-meter length scales 3-6 , with a dc sensitivity in the tens of pT/Hz 1/2 range 7 and even higher ac sensitivities 8 . At room temperature, the energy-level structure of the NV ground state is sensitive also to temperature fluctuations 9,10 ; a temperature change of 1 mK causes frequency shifts equivalent to a few-nT magnetic field change. Thus, the presence of noise in one of these quantities may impact the precision of measuring the other quantity unless there is a way of discerning them, for example by temporal signatures.The temperature of the diamond can be easily read out from the optically-detected magnetic resonance (ODMR) spectrum of the NV fluorescence by sweeping a microwave (MW) frequency around 2.8 GHz. The temperature is then inferred from the positions of two opposite spin transitions corresponding to the same crystallographic orientation 9 . Thermometry using pulsed MW protocols or cw -ODMR has been demonstrated with single NVs, nanodiamonds and bulk samples [11][12][13][14] . So far, temperature sensing was demonstrated for stationary or slowly-varying conditions at timescales of many seconds to hours. Large-range (±100 K) and high bandwidth temperature sensing has been shown in Ref. 15 requiring, however, averaging of thousands of measurements. This approach is therefore only suitable for the measurement of well-controlled transients.In this article, we report on a method for recording temperature transients on millisecond timescales in a single-shot measurement while being immune to the magnetic field that induces comparable resonance shifts. The scheme can also be reversed in order to record magnetic signals that are immune to temperature variations. Such temperature transients may be due to laser and/or MW signals operated in a quasi-continuous mode. Similar concepts have been introduced for pulsed MW schemes, a magnetometer immune to temperature drifts 16 and a thermometer insensitive to magnetic fields 11 .Our approach relies on the simultaneous driving of two transitions (m S = 0 ↔ m S = ±1) using cw, frequencyor amplitude-modulated MW fields with either the same or ...

Highlights Dopaminergic neurons dominate effective transverse relaxation in nigrosome 1. Ion beam microscopy reveals highest iron concentrations in dopaminergic neurons. Developed biophysical model links MRI parameters to cellular iron content. Ferritin- and neuromelanin-bound iron impact MRI parameters differently. Quantitative MRI provides a potential biomarker of iron in dopaminergic neurons.

Sensitive, real-time optical magnetometry with nitrogen-vacancy centers in diamond relies on accurate imaging of small (≪10), fractional fluorescence changes across the diamond sample. We discuss the limitations on magnetic field sensitivity resulting from the limited number of photoelectrons that a camera can record in a given time. Several types of camera sensors are analyzed, and the smallest measurable magnetic field change is estimated for each type. We show that most common sensors are of a limited use in such applications, while certain highly specific cameras allow achieving nanotesla-level sensitivity in 1 s of a combined exposure. Finally, we demonstrate the results obtained with a lock-in camera that paves the way for real-time, wide-field magnetometry at the nanotesla level and with a micrometer resolution.