The importance of diagnostic imaging is undisputable for those practicing medicine or those experiencing medical practice as patients or their families. Who could ever imagine modern clinical medicine without imaging techniques such as X‐ray radiography, computed tomography, ultrasound and magnetic resonance imaging? Even microscopy is widely known as an indispensable tool for diagnostic histopathology. It appears, however, less commonly known that imaging techniques have been and continue to be pivotal for pioneering research in biomedical sciences including physiology. Yet, throughout the history of biomedical research, innovative (imaging) techniques may even have had a greater impact on scientific progress than new scientific hypotheses per se.

A case in point in the early stages of biomedical research—or natural philosophy as it was called at this time—is light microscopy. Although still in its infancy, this technique enabled Robert Hooke (1635‐1703) to discern ‘cells’ in a thin slice of cork and, later on, also in ferns and sundews. Reminded of the cells in a honeycomb he coined this term accordingly and published his discoveries in a book aptly titled “Micrographia: Or some Physiological Descriptions of Minute Bodies made by Magnifying Glasses with Observations and Inquiries thereupon.“ (London, 1665) [emphasis added]. At around the same time (1661), Marcello Malpighi (1628‐1694) was the first who, via light microscopy, observed and correctly described capillaries—in a frog's lung! While the pulmonary circulation had been described much earlier by Ibn an‐Nafis (Arabic: ابن النفيس , c.1210‐1288), Realdo Colombo (1516‐1559) and Michael Servetus (Spanish: Miguel Serveto, 1509‐1553), Malpighi's discovery provided direct evidence for one pivotal aspect of the theory on blood circulation William Harvey (1578‐1657) had developed some 30 years earlier. Further corroboration of Harvey's theory came from observations of blood flowing through capillaries by Antonie van Leeuwenhoek (1632‐1723), also using the light microscope. Harvey's theory, published in his famous work “Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus” (Frankfurt, 1628), was no less than a complete paradigm shift in physiology vis‐à‐vis contemporary theories and beliefs still adhering to the writings of Galen of Pergamon (Greek: Γαληνός, 129‐c.216).

Today van Leeuwenhoek is remembered mainly as the first who documented microscopic observations of microbes. Light microscopic detection of various bacterial species in the 19th century paved the way for Robert Koch (1843‐1910). He proved that specific microbes are the cause of specific infections, earning him the 1905 Nobel Prize in Medicine and Physiology. Already then it was clear that infectious microbes must exist that are too small to be seen by the light microscope, but it took several decades before the electron microscope (EM) was invented to achieve the necessary spatial resolution. Helmut Ruska (1908‐1973) was the first to develop EM applications for biological specimens, based on inventions by Ernst Ruska (1906‐1988, 1986 Nobel Prize in Physics), Hans Busch (1884‐1973), Max Knoll (1897‐1969) and Reinhold Rüdenberg (1883‐1961). In 1940, Helmut Ruska published the first comprehensive description of viral structures. Since then, EM—with its refinements and developments (cf. 1986 Nobel Prize in Physics, 2017 Nobel Prize in Chemistry)—has become an invaluable tool in biomedical research. For physiologists, disruptive developments in light microscopy including intravital, multiphoton and fluorescence microscopy (cf. 2014 Nobel Prize in Chemistry) have also opened new research avenues. The combination of super‐resolved optical imaging at the level of single live cells, even single molecules, with single cell genomics including gene expression cartography,1 have become additional driving forces to probe (patho‐)physiology and molecular function in real time.

The early roots of non‐invasive imaging and diagnostic radiology date back to Wilhelm Conrad Röntgen (1845‐1923), who was the first to produce and detect X‐rays or Röntgen rays in 1895. This invention ultimately also led to Godfrey Hounsfield's (1919‐2004, 1979 Nobel Prize in Medicine and Physiology) development of computed tomography (CT) in 1973. Both X‐ray radiography and CT continue to be cornerstones of clinical diagnostics. At the same time, various biomedical research fields have utilized and continue to utilize X‐ray techniques. To name but one example, it was X‐ray crystallography that allowed Rosalind Franklin (1920‐1958) to obtain images of DNA that led to the famous description of the structure of the DNA and earned James Watson (b.1928), Francis Crick (1916‐2004) and Maurice Wilkins (1916‐2004) the 1962 Nobel Prize in Medicine and Physiology. Today, X‐ray crystallography, often in combination with other modern techniques such as cryo‐EM, is successfully employed to decipher structure‐function relationships of much smaller biomolecules. It is somewhat ironic that Röntgen's discoveries were awarded with the (very first) Nobel Prize in Physics (the 1901 Prize in Medicine and Physiology went to Emil von Behring), even though the X‐ray technology would have such a huge impact later on, both in clinical medicine as well as biomedical research.

The next giant step in the history of non‐invasive imaging took place about 80 years later, when Paul Lauterbur (1929‐2007) developed a method to encode spatial information into a nuclear magnetic resonance (NMR) signal. NMR had already been known, and used to study biological specimens, for several decades. However, Lauterbur's new method was the beginning of magnetic resonance imaging (MRI). Among other scientists, Sir Peter Mansfield (1933‐2017) pioneered advanced methods for MR image acquisition and processing (2003 Nobel Prize in Medicine and Physiology, jointly with Lauterbur). MRI scanners were first introduced into clinical medicine in the 1980s. Since then, MRI has experienced a plethora of technologic developments in hardware, imaging protocols and data processing, which have led to its widespread use in clinical medicine.2

Yet, MRI is, in current clinical practice, almost exclusively used to assess (pathological changes in) morphology only. MRI in (pre‐)clinical research, on the other hand, makes use of an ever broadening range of techniques that enable assessments of (physiological and pathophysiological changes in) various functional parameters. Probably the most prominent of these techniques is the so‐called blood oxygenation level–dependent (BOLD) MRI. This technique was introduced by Seiji Ogawa (b.1934) in 1990.2 BOLD MRI relies on the fact that deoxygenated haemoglobin (deoxyHb) is paramagnetic and, therefore, impacts on the effective transversal MR relaxation time T₂*. T₂* reflects the amount of deoxyHb per tissue volume, which can serve as a marker of blood oxygenation. Thus, BOLD MRI enables in vivo assessment of (changes in) blood oxygenation in real time; it is, furthermore, non‐invasive, and does not employ ionizing radiation. Upon its invention, BOLD MRI was immediately used to study patterns of neuronal activity in the brain. This was not surprising: for the first time in history, patterns of neuronal activity could be visualized in conscious humans!2 The approach is based on the paradigm that an increased local neuronal activity triggers an increase in local blood flow, which in turn decreases oxygen extraction of the blood perfusing the region, thereby lowering local deoxyHb.3 This led to the broad field of functional MRI that today is widely used to study temporal and spatial neuronal activity patterns within the brain during a plethora of (patho‐)physiologic conditions, tasks and paradigms.

An increasing number of BOLD studies have recently focussed on mechanisms of cardiovascular control. Thus, several studies aimed at further elucidating characteristics of the arterial baroreflex. Aside from methodological questions pertaining to its sensitivity,4, 5 the renewed interest in this reflex is driven by new approaches to treat resistant hypertension by means of baroreceptor stimulation, selective vagal nerve stimulation and deep brain stimulation.6 Brainstem nuclei are known to govern the arterial baroreflex, but this has hitherto been almost impossible to explore in living humans. A recent study that made use of advanced BOLD MRI of the human brainstem paves the way to further elucidate, non‐invasively, human cardiovascular control in health and disease.7 In another study in conscious humans, a dedicated BOLD technique demonstrated oscillations of cardiovascular parameters that are driven by central pacemaker activity in the brainstem.8

BOLD MRI continues to be a very valuable tool for preclinical studies that focus on pathophysiologies of cardiovascular control and potential new treatment options. Papers published in Acta Physiologica provide prime examples for the use of BOLD MRI in these research areas. For instance, BOLD measurements in spontaneously hypertensive rats showed that the lack of gut microbiome‐derived butyrate influences the activity of cardio‐regulatory brain regions; this led to the hypothesis that microbial butyrate may play a role in blood pressure regulation.9 In a rat model of ischemic stroke, dedicated functional MRI techniques were used in a longitudinal study to assess the benefit of early inhibition of the mitogen‐activated protein kinase 1/2 administered at a clinically relevant time point.10 As a non‐invasive technique, functional MRI complements various other ‘classical’ methods used to study cardiovascular control, ranging from—mostly invasive—in vivo to ex vivo techniques such as Ca⁺⁺ imaging.9, 11, 12

Kidney MRI has taken a centre stage in biomedical research, making use of the unique opportunities provided by functional MRI, in particular, BOLD. This is motivated firstly by the pivotal role that renal tissue hypoperfusion and hypoxia are assumed to play in the pathophysiology of various kidney diseases and the constraints of ‘classical’ physiological methods in translational contexts.13-15 Several special features of renal haemodynamics and oxygenation make the kidneys exceptionally vulnerable to an imbalance between oxygen delivery and demand. They result—inter alia—in a major heterogeneity in tissue partial pressure of oxygen (pO₂) among the renal layers (cortex, outer medulla and inner medulla) with very low pO₂ in the medulla.

An ever increasing number of preclinical studies—many of which published in Acta Physiologica—indicate that renal tissue hypoxia is an important early element in the pathophysiology of acute kidney injury (AKI), its possible progression to chronic kidney disease (CKD) and diabetic nephropathy.12, 14, 16-20 Many of these studies utilized invasive probes to measure renal haemodynamics and oxygenation in anesthetized animals. The probes typically include Clark‐type electrodes or fluorescence optodes, ie gold standard methods for measurement of tissue pO₂. As local tissue pO₂ is quite heterogeneous even within a given renal layer, a significant drawback of these probes is that they obtain data within a rather small volume of tissue only.13 Here, BOLD MRI can play to its advantages: besides being non‐invasive, it enables whole kidney coverage and high spatial resolution.15 Consequently, BOLD is increasingly used in preclinical studies that aim at elucidating renal (patho‐)physiology as well as testing potential measures for prevention or therapy of renal disorders. For example, by means of BOLD it was demonstrated that specific pharmacological interventions targeting the cytochrome p450 (CYP)‐eicosanoid pathway in renal ischaemia/reperfusion injury alleviates renal tissue hypoxia in rats.19 The translational importance of this result is underlined by findings in humans indicating that individual differences in CYP eicosanoid formation may contribute to the risk of developing AKI.19 In the majority of studies on animal models of renal diseases, BOLD data are complemented by other methods including, but not limited to, standard histology, EM, renal tissue‐, blood‐ and urine‐based biomarkers, and X‐ray CT.12, 15, 18, 19

The second motivation to promote functional renal MR is the notorious lack of clinically available diagnostic tools that would allow early recognition of AKI and CKD, with sufficient sensitivity and specificity. In today's clinical practice, diagnosis of these disorders still relies on serum concentrations of creatinine. Although an ever increasing number of new blood‐ or urine‐based biomarkers have been proposed, neither has hitherto advanced to provide point‐of‐care diagnosis for AKI. The early detection of AKI and, thus, the opportunity for the timely care for patients suffering from AKI, is widely recognized as a major unmet clinical need. Synergistic approaches that include functional renal MRI have been proposed to meet that need. Consequently, an increasing number of studies in humans evaluate the potential of renal MRI including BOLD as diagnostic tools for AKI and CKD.15, 21 Yet, to become clinically relevant as quantitative biomarker(s), functional renal MRI protocol(s) still require standardization with regard to physiological conditions and technical parameters. Last but not least, as a number of factors confound the renal T₂* to tissue pO₂ relationship, their quantitative impact in various (patho‐)physiological scenarios must be determined.15

As the present short review illustrates, there can be no doubt that imaging techniques have had and continue to have a pivotal role in biomedical sciences including physiologic research. Images are generally highly impressing and convincing, and as the saying goes: seeing is believing. Yet, we should remain cautious to take results based on imaging (alone) at face value. Unintentional errors, inconsiderately overstated interpretations, and in some cases even fraud, are known to have occurred.

An early and (in‐)famous case in point is Ernst Haeckel‘s (1834‐1919) depiction of embryos of various vertebrates in his book “Natürliche Schöpfungsgeschichte” (Berlin, 1868). He was justifiably accused to have ‘embellished’ these images in his attempt to support Charles Darwin's (1809‐1882) theory of evolution in what is regarded as one of the most heated debates in (natural‐)philosophy of all times. Copyright infringement could be considered an additional reproach for Haeckel's work in today's terms, even though copying images was not yet generally regarded as serious scientific misconduct in the 19th century. However his, at least marginally, fraudulent images are still misused today as foundation to disavow the theory of evolution.22

Another (in‐)famous publication in 2009 reporting on a dead salmon's brain ‘answering’ when ‘asked’ to perform a social perspective taking according to an established paradigm appeared at first glance to merely ridicule BOLD MRI. On the contrary, this publication was a wake‐up call for appropriate processing of BOLD data and its duly cautious interpretation.23 The necessity to careful interpret BOLD results was recently reiterated by a study in mice. Using ‘classical’ physiological methods to monitor cardiovascular parameters, the study demonstrated that a major portion of changes in brain BOLD data in an established somatosensory paradigm is induced by changes in arterial blood pressure rather than changes in neuronal activity.3

To conclude, the biomedical research community, and physiologists in particular, should be aware that promoting innovative imaging techniques across multiple scales in space and time is essential for the study of biological systems and disease. On the other hand, the community should also be aware that developing robust imaging tools and promoting the reproducibility and careful interpretation of imaging findings are equally essential. This includes the necessity of more critical evaluation of intriguing images as well as the conclusions derived from these images by means of other research methods especially those originating from ‘classical’ physiology. The findings obtained by this approach should be integrated with (big) data science, including artificial intelligence, predictive analysis and deep machine learning into a coherent picture of cells, tissues, organs and organisms for a better understanding of (patho‐)physiology. With this exceptional level of innovation and rich opportunity for discovery, we cannot imagine physiology without imaging.

诊断成像的重要性对于行医者或作为患者或其家属进行医疗实践的人来说是无可争议的。如果没有 X 射线摄影、计算机断层扫描、超声和磁共振成像等成像技术，谁能想象现代临床医学？甚至显微镜也被广泛认为是诊断组织病理学不可或缺的工具。然而，似乎鲜为人知的是，成像技术一直并将继续对包括生理学在内的生物医学科学的开创性研究发挥关键作用。然而，纵观生物医学研究的历史，创新（成像）技术对科学进步的影响甚至可能比新的科学假设本身更大。

生物医学研究早期阶段的一个例子——或者当时称为自然哲学——是光学显微镜。尽管仍处于起步阶段，但这项技术使罗伯特·胡克 (Robert Hooke，1635-1703) 能够辨别软木薄片中的“细胞”，后来也辨别出蕨类植物和毛毡苔中的“细胞”。想起蜂窝中的细胞，他相应地创造了这个术语，并将他的发现发表在一本书中，标题恰如其分：“显微术：或放大镜制作的微小物体的一些生理学描述，随后进行了观察和查询。”（伦敦，1665 年）[强调添加]。大约在同一时间（1661 年），马塞洛·马尔皮吉（Marcello Malpighi，1628-1694 年）是第一个通过光学显微镜，观察并正确描述毛细血管——在青蛙的肺中！虽然 Ibn an-Nafis（阿拉伯语：ابن النفيس，c.1210-1288）、Realdo Colombo（1516-1559）和 Michael Servetus（西班牙语：Miguel Serveto，1509-1553），Malpighi 的发现更早地描述了肺循环为大约 30 年前威廉·哈维（William Harvey，1578-1657）发展起来的血液循环理论的一个关键方面提供了直接证据。Harvey 理论的进一步证实来自 Antonie van Leeuwenhoek (1632-1723) 对血液流经毛细血管的观察，同样使用光学显微镜。Harvey 的理论，发表在他的著名著作“Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus”中（法兰克福，1628 年），这不亚于生理学相对于当代理论和信仰的彻底范式转变，仍然坚持佩加蒙的盖伦（希腊语：Γαληνός，129-c.216）的著作。

今天，van Leeuwenhoek 主要被人们铭记为第一个记录微生物微观观察的人。19 世纪对各种细菌物种的光学显微镜检测为 Robert Koch (1843-1910) 铺平了道路。他证明了特定微生物是特定感染的原因，为他赢得了 1905 年的诺贝尔医学和生理学奖。那时已经很明显，必须存在太小而无法被光学显微镜看到的传染性微生物，但是电子显微镜 (EM) 的发明花了几十年时间才能达到必要的空间分辨率。Helmut Ruska (1908-1973) 基于 Ernst Ruska (1906-1988，1986 年诺贝尔物理学奖)、Hans Busch (1884-1973)、Max Knoll (1897-1969) 的发明，率先开发了生物标本的 EM 应用) 和 Reinhold Rüdenberg (1883-1961)。1940 年，Helmut Ruska 首次发表了对病毒结构的全面描述。从那时起，EM 凭借其改进和发展（参见 1986 年诺贝尔物理学奖、2017 年诺贝尔化学奖）已成为生物医学研究的宝贵工具。对于生理学家来说，包括活体显微镜、多光子显微镜和荧光显微镜在内的光学显微镜的颠覆性发展（参见 2014 年诺贝尔化学奖）也开辟了新的研究途径。将单个活细胞甚至单个分子水平的超分辨光学成像与包括基因表达图谱在内的单细胞基因组学相结合，2017 年诺贝尔化学奖）——已成为生物医学研究的宝贵工具。对于生理学家来说，包括活体显微镜、多光子显微镜和荧光显微镜在内的光学显微镜的颠覆性发展（参见 2014 年诺贝尔化学奖）也开辟了新的研究途径。将单个活细胞甚至单个分子水平的超分辨光学成像与包括基因表达图谱在内的单细胞基因组学相结合，2017 年诺贝尔化学奖）——已成为生物医学研究的宝贵工具。对于生理学家来说，包括活体显微镜、多光子显微镜和荧光显微镜在内的光学显微镜的颠覆性发展（参见 2014 年诺贝尔化学奖）也开辟了新的研究途径。将单个活细胞甚至单个分子水平的超分辨光学成像与包括基因表达图谱在内的单细胞基因组学相结合，1已成为实时探测（病理）生理学和分子功能的额外驱动力。

无创成像和诊断放射学的早期根源可以追溯到 Wilhelm Conrad Röntgen (1845-1923)，他是 1895 年第一个产生和检测 X 射线或 Röntgen 射线的人。这项发明最终也导致了 Godfrey Hounsfield (1919) ‐2004 年，1979 年诺贝尔医学和生理学奖）1973 年计算机断层扫描 (CT) 的发展。X 射线 X 射线照相术和 CT 仍然是临床诊断的基石。与此同时，各种生物医学研究领域已经利用并继续利用 X 射线技术。仅举一个例子，正是 X 射线晶体学使 Rosalind Franklin (1920-1958) 获得了 DNA 的图像，从而导致了对 DNA 结构的著名描述，并赢得了 James Watson (b.1928)，弗朗西斯·克里克 (1916-2004) 和莫里斯·威尔金斯 (1916-2004) 获得 1962 年诺贝尔医学和生理学奖。今天，X 射线晶体学通常与其他现代技术（如冷冻电镜）相结合，成功地用于破译更小的生物分子的结构 - 功能关系。具有讽刺意味的是，伦琴的发现获得了（第一个）诺贝尔物理学奖（1901 年医学和生理学奖颁给了埃米尔·冯·贝林），尽管 X 射线技术后来会产生如此巨大的影响，无论是在临床医学还是生物医学研究。

大约 80 年后，无创成像历史上的下一个巨大进步发生了，当时 Paul Lauterbur (1929-2007) 开发了一种将空间信息编码为核磁共振 (NMR) 信号的方法。几十年来，核磁共振已经为人所知，并用于研究生物标本。然而，劳特伯的新方法是磁共振成像 (MRI) 的开端。在其他科学家中，彼得·曼斯菲尔德爵士（Sir Peter Mansfield，1933-2017 年）开创了先进的 MR 图像采集和处理方法（2003 年与劳特伯共同获得诺贝尔医学和生理学奖）。MRI 扫描仪于 1980 年代首次引入临床医学。从那时起，MRI 在硬件、成像协议和数据处理方面经历了大量的技术发展，这导致其在临床医学中得到广泛应用。2

然而，在当前的临床实践中，MRI 几乎仅用于评估形态学（病理变化）。另一方面，（前）临床研究中的 MRI 使用范围不断扩大的技术，可以评估（生理和病理生理变化）各种功能参数。这些技术中最突出的可能是所谓的血氧水平依赖性 (BOLD) MRI。该技术由 Seiji Ogawa (b.1934) 于 1990 年引入。2 BOLD MRI 依赖于脱氧血红蛋白 (deoxyHb) 是顺磁性的这一事实，因此会影响有效的横向 MR 弛豫时间 T ₂ *。Ť ₂* 反映每组织体积的脱氧血红蛋白量，可作为血液氧合的标志物。因此，BOLD MRI 能够实时在体内评估血氧合（变化）；此外，它是非侵入性的，并且不使用电离辐射。BOLD MRI 一经发明便立即用于研究大脑中神经元活动的模式。这并不奇怪：历史上第一次可以在有意识的人类中看到神经元活动的模式！2该方法基于这样一种范式，即局部神经元活动的增加会触发局部血流量的增加，从而减少灌注该区域的血液的氧气提取，从而降低局部脱氧血红蛋白。3这导致了功能 MRI 的广泛领域，如今该领域被广泛用于研究在过多（病理）生理条件、任务和范式期间大脑内的时间和空间神经元活动模式。

最近越来越多的 BOLD 研究集中在心血管控制机制上。因此，一些研究旨在进一步阐明动脉压力反射的特征。除了与其敏感性有关的方法学问题4, 5 之外，通过压力感受器刺激、选择性迷走神经刺激和脑深部刺激治疗顽固性高血压的新方法，也推动了对这种反射的新兴趣。6众所周知，脑干核控制着动脉压力反射，但迄今为止，这几乎不可能在活人身上进行探索。最近一项利用人类脑干的先进 BOLD MRI 的研究为进一步阐明人类心血管在健康和疾病中的无创控制铺平了道路。7在另一项针对有意识的人类的研究中，一项专门的 BOLD 技术证明了由脑干中的中央起搏器活动驱动的心血管参数的振荡。8

BOLD MRI 仍然是临床前研究非常有价值的工具，这些研究侧重于心血管控制的病理生理学和潜在的新治疗方案。Acta Physiologica 上发表的论文为 BOLD MRI 在这些研究领域的使用提供了主要示例。例如，自发性高血压大鼠的 BOLD 测量表明，缺乏肠道微生物组衍生的丁酸盐会影响心脏调节大脑区域的活动；这导致了微生物丁酸盐可能在血压调节中发挥作用的假设。9在缺血性中风大鼠模型中，在纵向研究中使用了专门的功能性 MRI 技术来评估在临床相关时间点早期抑制丝裂原活化蛋白激酶 1/2 的益处。10作为一种非侵入性技术，功能性 MRI 补充了用于研究心血管控制的各种其他“经典”方法，范围从（主要是侵入性的）体内到体外技术，例如 Ca ⁺⁺成像。9、11、12

肾脏 MRI 已成为生物医学研究的中心，利用功能性 MRI，尤其是 BOLD 提供的独特机会。这首先是由于肾组织低灌注和缺氧在各种肾脏疾病的病理生理学中发挥的关键作用以及“经典”生理学方法在转化环境中的限制。13-15肾脏血流动力学和氧合的几个特殊特征使肾脏特别容易受到氧气输送和需求之间的不平衡的影响。它们result-尤其在组织-in一大的异质性的氧分压（PO ₂肾层中具有非常低的PO）（皮质，外髓质和内髓质）₂ 在髓质中。

越来越多的临床前研究（其中许多发表在Acta Physiologica 上）表明，肾组织缺氧是急性肾损伤 (AKI) 病理生理学的重要早期因素，它可能发展为慢性肾病 (CKD) 和糖尿病肾病. 12, 14, 16-20其中许多研究使用侵入性探针来测量麻醉动物的肾脏血流动力学和氧合。探针通常包括克拉克型电极或荧光光极，即测量组织 pO _{2 的}金标准方法。由于局部组织 pO ₂即使在给定的肾层内也非常不均匀，这些探针的一个显着缺点是它们仅在相当小的组织体积内获得数据。13在这里，BOLD MRI 可以发挥其优势：除了无创外，它还可以覆盖整个肾脏和高空间分辨率。15因此，BOLD 越来越多地用于旨在阐明肾脏（病理）生理学以及测试预防或治疗肾脏疾病的潜在措施的临床前研究。例如，通过 BOLD 证明，针对肾缺血/再灌注损伤中细胞色素 p450 (CYP)-类二十烷酸通路的特定药理学干预可缓解大鼠肾组织缺氧。19在人类中的发现强调了这一结果的转化重要性，表明 CYP 类二十烷酸形成的个体差异可能导致发生 AKI 的风险。19在大多数关于肾脏疾病动物模型的研究中，BOLD 数据得到了其他方法的补充，包括但不限于标准组织学、EM、基于肾组织、血液和尿液的生物标志物以及 X 射线 CT。12、15、18、19

促进功能性肾脏 MR 的第二个动机是众所周知的缺乏临床可用的诊断工具，这些工具可以使 AKI 和 CKD 的早期识别具有足够的敏感性和特异性。在今天的临床实践中，这些疾病的诊断仍然依赖于肌酐的血清浓度。尽管已经提出了越来越多的新的基于血液或尿液的生物标志物，但迄今为止还没有一种能够为 AKI 提供即时诊断。AKI 的早期检测，从而为 AKI 患者提供及时护理的机会，被广泛认为是尚未满足的主要临床需求。已经提出了包括功能性肾 MRI 在内的协同方法来满足这一需求。因此，15, 21然而，要成为临床相关的定量生物标志物，功能性肾脏 MRI 协议仍然需要在生理条件和技术参数方面进行标准化。最后但并非最不重要的一点是，由于许多因素混淆了肾脏 T ₂ * 与组织 pO _{2 的}关系，因此必须确定它们在各种（病理）生理情况下的定量影响。15

正如本文的简短评论所示，毫无疑问，成像技术已经并将继续在包括生理研究在内的生物医学科学中发挥关键作用。图像通常非常令人印象深刻和令人信服，俗话说：眼见为实。然而，我们应该保持谨慎，对基于图像（单独）的结果进行表面价值评估。众所周知，无意的错误、过分夸大的解释，在某些情况下甚至是欺诈。

Ernst Haeckel (1834-1919) 在他的书“ Natürliche Schöpfungsgeschichte”（柏林，1868 年）中对各种脊椎动物胚胎的描述是一个早期的（不知名的）例子。他被指控“美化”了这些图像，以支持查尔斯·达尔文（1809-1882）的进化论，这是有史以来（自然-）哲学中最激烈的辩论之一。尽管在 19 世纪复制图像尚未被普遍视为严重的科学不端行为，但在今天的术语中，侵犯版权可以被视为对海克尔作品的额外谴责。然而，他的（至少是轻微的）欺骗性图像今天仍然被滥用作为否定进化论的基础。22

2009 年另一篇（不知名的）出版物报道了一条死鲑鱼的大脑在“被要求”根据既定的范式进行社会视角的“回答”时，乍一看似乎只是在嘲笑 BOLD MRI。相反，该出版物为适当处理 BOLD 数据及其适当谨慎的解释敲响了警钟。23最近一项小鼠研究重申了仔细解释 BOLD 结果的必要性。该研究使用“经典”生理方法来监测心血管参数，表明在已建立的体感范式中，大脑 BOLD 数据的大部分变化是由动脉血压的变化而不是神经元活动的变化引起的。3

总而言之，生物医学研究界，尤其是生理学家，应该意识到在空间和时间的多个尺度上推广创新的成像技术对于生物系统和疾病的研究至关重要。另一方面，社区也应该意识到开发强大的成像工具和促进成像结果的可重复性和仔细解释同样必不可少。这包括对有趣的图像以及通过其他研究方法从这些图像得出的结论进行更批判性评估的必要性，尤其是那些源自“经典”生理学的研究方法。通过这种方法获得的发现应与（大）数据科学相结合，包括人工智能、预测分析和深度机器学习到细胞、组织、器官和生物体的连贯图片中，以更好地理解（病理）生理学。凭借这种非凡的创新水平和丰富的发现机会，我们无法想象没有成像的生理学。