大脑的数字孪生：让你聪明一世

来源：升华洞察

作者：冯升华

本文摘要（由AI生成）：

本文介绍了人脑数字双胞胎的概念，以及其在预防和治疗神经退行性疾病方面的潜力。文章通过引用达索系统虚拟人体建模的高级总监Stephen Levine博士的演讲分享，介绍了虚拟双胞胎在医疗保健领域的最新进展。文章还介绍了创伤性脑损伤的模拟模型，以及开颅减压术的案例分享。此外，文章还讨论了经颅直流电刺 激治疗精神分裂症和特定患者治疗优化的问题。最后，文章提到了云端的数字双胞胎。

如果我们有了人脑的数字双胞胎，是否可以消除各种与智力和神经有关的疾病？那人类就将聪明一世了。本文将介绍这一领域的最新进展。

本文选译自达索系统虚拟人体建模的高级总监Stephen Levine博士在GEN（Genetic Engineering & Biotechnology News）举办的Webinar的演讲分享《通过大脑的虚拟双胞胎来预防痴呆》。

I'm Steve Levine and I lead virtual human modeling Dassault Systemes. On this webinar, I am going to share some of my experiences with this new approach to healthcare, and there are a number of examples why we believe the concept of the virtual twin can transform the development, approval and even the treatment protocols for many modern challenges in health care. Including the treatment of neuro degenerative diseases.

我是史蒂夫·莱文（Steve Levine），是达索系统公司虚拟人体建模的负责人，在这次网络研讨会上，我将分享我在使用这种新的医疗保健方法方面的一些经验，并且有许多例子使我们相信人体数字双胞胎可以改变医疗保健中面向许多现代挑战的开发、批准甚至治疗方案，包括神经退行性疾病的治疗。

Here's the agenda for today's talk, First I'll provide a brief introduction to mycompany, our history, motivation, and our vision for the transformative potential of digital technology developing personalized or precision treatments. Next, I’ll describe our first deep investigation into what we call the virtual twin experience. Through the creation of the ‘living heart’ project, where we took on the challenge of building a fully functional virtual heart using what we learned from that, I will share the development and some applications of a virtual brain, and then we'll open the phone for Q&A.

这是今天演讲的议程，首先，我将简要介绍我们公司，公司的历史、动机以及我们对数字技术开发个性化或精准医疗的变革潜力的愿景。接下来，我将描述我们对所谓的虚拟双胞胎体验的首次深入研究。通过创建“活体心脏”项目，我们从中学到的知识来构建功能全面的虚拟心脏的挑战，我将分享虚拟大脑的开发和一些应用，然后打开手机进行问答环节。（第一、二部分略，今天我们只讲第三部分：人脑的数字双胞胎）

Hopefully that's given you some idea ofthe rapid advances that we've been able to make through the methodology of the living heart project, that's allowed us a much deeper understanding of human physiology and building a method to collaborate and capture the best knowledge that humans have to offer.

希望这使您对我们通过“活体心脏”计划的方法所取得的快速进步有所了解，这使我们对人类生理学有了更深的了解，并建立了一种协同并捕获人类最佳知识的方法。

So taken what we've learned in the living heart project we have begun to explore the development of the living brain model, while we have much more to go, as you'll see already, we have a range of applications that we can already address which you are giving us confidence for the future, so let me feel a few of these few these examples.

因此，根据我们在“活体心脏”项目中所学到的知识，我们开始探索“活体大脑”模型的发展，尽管我们还有很多工作要做，正如您已经看到的那样，我们已经拥有了许多应用，使我们对未来充满信心，让我们来感受一下这些例子中的一些典型。

I've broken the examples down into three different types of treatment simulations, the first represents the use of brain models to explore damage done to the brain as a result of physical phenomena such as traumatic brain injury and surgical interventions. The next examples involve patient specific guidance for neuromodulation, the final there are some exciting new research into predicting neuro degenerative disease progression. 

我将这些示例分为三种不同的治疗方案仿真，第一种代表使用大脑模型来探索由于诸如创伤性脑损伤和外科手术等物理现象对大脑造成的损害，接下来的例子涉及指导对特定患者的神经调节，最后还有一些激动人心的新研究可以预测神经退行性疾病的发展。

First I will discuss traumatic brain injury or TBI, as you probably know is a widespread condition considered to be any non-degenerative or non-congenital intrusion into the brain from an external mechanical force. This mechanical force can lead to temporary or even permanent impairment of cognitive, physical, or psychological functions. 

首先，我将讨论创伤性脑损伤或TBI，您可能已经知道这是一种广泛的疾病，TBI被认为是外部机械力对大脑的任何非变性或非先天性侵入。这种机械力可能导致认知、身体或心理功能的暂时甚至永久性损害。

When we first developed the brain model, in fact an entire head and neck model who was done in collaboration with our partners at synopsis, Simplewear and the naval research labs, who are obviously interested in understanding how to protect soldiers from blasts at all scales. 

当我们首次开发大脑模型时，实际上是与Simplewear公司、海军研究实验室等合作伙伴合作完成的整个头部和颈部模型，他们显然对了解如何保护士兵免受各种规模的爆炸非常感兴趣。

Of course, TBI can occur from many sources and affect many different regions of the brain as with the living heart, our goal is to develop horizontally deployable models that are not so finely tuned that they would be only limited to individual use cases. We're all very familiar with injuries from sports such as direct impact in professional football and the rapid deceleration from automotive crashes, but some of our greatest challenges for how to protect our soldiers. For example, the recent strike in the US camps in Iraq we know there's already more than 100 soldiers who suffered from TBI. 

当然，TBI可能有许多来源，会影响大脑的许多不同区域，就像我们之前研究的“活体心脏”一样。我们的目标是开发可部署水平的模型，这些模型的调整可能并不那么精细，以致仅局限于个别应用场景。我们对运动造成的伤害非常熟悉，例如对职业橄榄球的直接撞击以及由于撞车而导致的快速减速，但我们面临的最大挑战在于如何保护我们的军队的士兵。例如，最近美国在伊拉克的军营遭受导弹袭击的事件，据报道已经有100多名美军士兵遭受了TBI的折磨。

I'll briefly describe two examples, one from a direct impact. And the other from frontal blast pressure wave, as you can see, the impact scenarios for each case are very different than the one impact profile is much broader and the location is centralized, in the other, the pressure wave moves more rapidly in just a few milliseconds, so I’ll go through each analysis. 

我将简要描述两个示例，其中一个是直接撞击的情况，另一种来自正面爆炸压力波的情况，直接冲击情景中冲击曲线大不相同，且位置集中的情况大不相同；而在另一种情况下，压力波移动得更快，仅仅几毫秒的时间，我将分析两种情况。

Developing the head neck model follows more or less the same procedure as with the heart, the model begins with clinical image data, is transformed into 3D geometry and then segmented into the necessary functional elements of the head. Each segment then is assigned the physical properties of a real head, which are derived based primarily on cadaver testing. 

开发头颈部模型的过程与“活体心脏”模型开发过程大致相同，从临床图像数据开始，转换为3D几何形状，然后细分头部的必要功能元素。然后为每个部分分配一个真实头部的物理属性，这些属性主要基于对尸体的测试得出。

For this model, the properties we have really only represent the physical characteristics necessary to reproduce the physical environment, interpreting the psychological impact of brain function from the impact would require a far more detailed model. And not considered for this analysis. 

Even so, the model requires 30,000,000 degrees of freedom and can only be run over a very short period of time. 

对于这个头部模型，我们拥有的属性实际上仅代表了再现物理环境所必需的物理特征，从这种影响来解释脑功能的心理影响将需要更详细的模型。在这个案例中并没有考虑进行此分析。即使这样，该头部模型仍需要30,000,000个自由度，并且只能在很短的时间内运行。

This slide shows the details of the 3D head simulation model, although relatively small in comparison to something, say like a commercial jet. It's also quite complex, and therefore we need on the order of three and a half million elements, to describe the full detail of the human head and the brain. Representing a 33 different anatomical structures, each individually represented so they could be analyzed independently. 

这张幻灯片显示了3D头部仿真模型的详细信息，尽管与诸如商用喷气式飞机之类的东西相比，它相对较小，但这个模型也非常复杂，我们需要大约三百五十万个单元来描述人的头部和大脑的全部细节。模型表达了33种不同的解剖结构，每个结构分别表达，因此可以对其进行独立分析。

The model is then accelerated to an impact at 45 degree angle. On the right, you can see the results showing the validation data for the pressures created inside the simulation as compared with those that are measured in a cadaveric. As you can see, the model shows good correlation with the measured data. Now, of course, that the model here is not limited to the single scenario, it can easily be modified to increase or decrease its fidelity. You can alter the scenario could include details such as a complete set of neck muscles or head protection or impact from really any angle. 

然后将模型变为呈45度角的撞击。在右侧您可以看到结果，其中显示了验证数据,在仿真模型中创建的压力与在尸体中测量的压力相比的结果。如您所见，该模型与测量数据显示出良好的相关性。当然，这里的模型并不局限于单个场景，可以轻松地对其进行修改以增加或降低其保真度。您可以更改场景，包括细节，例如完整的颈部肌肉或头部保护，或实际上可以从任何角度进行撞击。

Here in this video you can see the improved view using our 3D experience platform, which also highlights how much more intuitive it is to see these phenomenon represented in full three dimensions. 

在此视频中，您可以使用我们的三维体验平台查看经过改进的视图，该平台还突出显示了以直观的全三维表示这些现象。

Moving on now I’ll go through another example of TBI. In this case, from a blast loading as represented by a frontal shock wave, here we see the experimental setup for calibrating and testing the virtual model. These results are reported in a paper indicated at the upper right you can see the experimental rig can provide invaluable data for quantities that are readily measured, whereas simulation allows you to dig much deeper into what's happening on the inside. 

我现在将继续介绍TBI的另一个示例。在这个案例中，从正面冲击波所代表的爆炸载荷中，我们看到了用于校准和测试虚拟模型的实验装置。这些结果报告在右上角显示的论文中，您可以看到实验装置可以为易于测量的数量提供宝贵的数据，而模拟则可以让您更深入地了解内部发生的事情。

In the case of a blast loading, the impact is very rapid and the shockwave passes in a few milliseconds. We can see, however, that the compressive wave actually travels through the skull faster than the wave surrounding the skull out in free air. This creates a negative pressure system at the back of the head, which is actually reduced very well by the model, as shown in the graph in the upper right where we compare the measured pressure against that of the simulation. 

在爆炸载荷的情况下，冲击非常迅速，冲击波会在几毫秒内通过。但是，我们可以看到，压缩波实际上比在自由空气中围绕头骨的波传播的快得多。这将在头部后部造就一个负压系统，实际上该模型可以很好地降低该负压系统，如右上图所示，我们将测得的压力与模拟压力进行了比较。

Once again, we get good validation and are able to actually dig more deeply into what's happening inside the head once we know we've reproduced the overall behavior correctly. 

我们再次得到了很好的验证，并且一旦知道我们正确地再现了整体行为，就能够更深入地研究头部内部的情况。

Here we show the blast wave traveling through the head from both the external region as well as a mid-sagittal region. Once again you can observe peak pressures near the base of the brain as the wave passes through. Looking more deeply into the brain itself, the affirmations in the skull which I haven't actually shown here, result in peak strains in the centerline of the brain, which most likely correspond to strains that would exceed the injury level. 

在这里显示了爆炸波从外部区域以及中矢状区域穿过头部传播。再一次，您可以在波通过时观察到靠近大脑底部的峰值压力。更深入地观察大脑本身，我在这里没有实际显示，头骨中确认在大脑中心线产生峰值应变，这很可能对应于超过损伤水平的应变。

My next case study is actually a clinical treatment simulation that might be used in a severe case of TBI or other brain trauma that would lead to excess pressure build up inside the skull. In Decompressive Craniectomy, a surgeon will give space to the brain to allow outward herniation, which would prevent compression of the brain stem structures or reconstructive brain perfusion. 

我的下一个案例研究实际上是临床治疗模拟，可用于严重的TBI或其他脑部创伤，这会导致颅骨内积压过多。在减压性颅骨切除术中，外科医生会给大脑留出空间以允许向外突出，这将防止脑干结构受压或重建性脑灌注。

Decompressive Craniectomy, although it can be very effective, remains a controversial surgical procedure with high failure rates as it induces large mechanical strains which may be the cause of brain damage later. This work from collaborators at Stanford, Exeter and Oxford universities, the authors attempt to quantify the strains in the brain from a personalized craniotomy treatment. 

减压颅骨切除术虽然非常有效，但仍引起争议，手术失败率很高，因为它会引起较大的机械应变，这可能是以后脑部损伤的原因。这项工作是由斯坦福大学，埃克塞特大学和牛津大学的合作者完成的，作者试图通过个性化的颅骨切开术治疗来量化大脑中的压力。

The simulations can reveal potential failure mechanisms, stretch, compression, and shear, and identify the regions of highest risk for brain damage to guide the surgeon in his procedure. For this model, the authors used 190 different scans, each at zero point nine millimeter intervals, which were taken from an ad ult female volunteer which were used to create the model. 

这次仿真可以揭示潜在的失效机制、拉伸、压缩和剪切，并确定发生脑损伤的最高风险区域，以指导外科医生进行手术。对于该模型，作者使用了190个不同的扫描，每个扫描的层间间隔均为9毫米，这些扫描来自用于创建模型的成年女性志愿者。

Given the novelty of this analysis, the authors looked at this procedure and studied it with varying degrees of fidelity of the model to explore the sensitivity to the levels of detail, and ultimately optimized the model efficiency. 

鉴于这种分析的新颖性，作者研究了此过程，并以不同的模型逼真度对其进行了研究，以探索对细节水平的敏感性，并最终优化了模型效率。

In the simplest model only hyperelastic tissue is used to represent the brain, with unique properties for both white and gray matter, in a model that had about 1.3 million elements. In the poroelastic model, white and gray matter is represented as more of a saturated medium, which includes velocity fluidic effects such as permeability welding and capillary effects. Much more realistic model, but far more computational in demanding. 

在最简单的模型中，仅使用超弹性组织来代表大脑。在具有约130万个单元的模型中，白质和灰质具有独特的属性。在孔隙弹性模型中，白质和灰质表示为更多的饱和介质，其中包括速度流体效应，例如渗透性融合率和毛细血管效应。更接近现实的模型则需要更多的计算。

I don't have time to go once again into the details, but here you can see an overview of the simulation methodology, and an example of the results. The craniotomy was simulated by removal of about ten centimeter diameter section of the less left posterior skull. Friction contact was then used between the brain and the fluid. Inside the skull, which was shown in the pink section above, which allows the brain the freedom to expand in response to release of the intracranial pressure. On the right, we could see a systematic analysis of the displacement, the strains, and the stretching at different degrees of swelling, which vary from about 2% to 10% at 2% intervals. 

我没有时间再详细介绍，但是在这里您可以看到仿真方法的概述以及结果示例。开颅手术是通过切除左后颅骨约十厘米直径的部分来模拟的。然后在大脑和脑基液之间使用摩擦接触。在头骨内部，如上面的粉红色部分所示，它使大脑能够自由响应颅内压的释放而扩展。在右侧，我们可以看到在不同溶胀度下的位移、应变和拉伸的系统分析，它们以2％的间隔在大约2％到10％之间变化。

What we can see is the axons located right at the leading edge of the opening are at the highest risk to the tangential stretching forces. Here is a 3D representation provided by the authors which actually give you a little more insight into the understanding of the analysis. 

我们可以看到，位于开口前边缘的轴突承受切向拉伸力的风险最高。这是作者提供的3D表达，它实际上使您对分析的理解有了更多的了解。

My next set of application examples are of 3D guided neuromodulation, as I'm sure you know the brain is highly affected by externally applied or induced electrical signals and these treatments, sometimes called electrolysis articles, can offer life changing opportunities. The treatments fall into two categories. Invasive, which involves embedding electrodes directly into the brain and non-invasive, where external simulation is applied outside the skull. 

我的下一组应用示例是3D引导的神经调节，我确定您知道大脑会受到外部施加的或感应的电信号的高度影响，而这些疗法（有时称为电刺 激）可以为患者提供改变生活的机会。疗法分为两种类别：有创的，包括将电极直接嵌入大脑，以及无创的，其中在颅骨外应用外部模拟。

Because it has the most precise delivery, deep brain stimulation or DBS is the most common today, however there remain still remain many challenges and risks. So let me show you some of the work we've done on DBS. 

因为深层刺 激或DBS是最精确的递送方式，所以在今天是最常见的，但是仍然存在许多挑战和风险。这里我向您展示我们在DBS（脑深部电刺 激术）上所做的一些工作。

DBS is already a well established therapy, for example, for the control of motor symptoms in Parkinson’s disease, but there are several critical aspects of DBS to be effective. One is the appropriate targeting, an accurate placement of the DBS lead location and the stimulation and the precise program delivery of electrical energy impulses. Most of our focus to date has been on the former using the methodologies to reconstruct the head and brain to guide the surgeon. 

DBS已经是一种成熟的疗法，例如，用于控制帕金森氏病中的运动症状，但是DBS有几个关键方面有效。一种是适当的目标定位，DBS引线位置的准确放置以及电能脉冲的刺 激和精确程序传递。迄今为止，我们的大部分注意力都集中在使用方法重建头部和大脑以指导外科医生的方法上。

We've worked with a company called Neurotargeting which has developed an Atlas that can be used as a roadmap for a surgeon to understand the likely areas of critical function which are based on a population analysis. These maps can then be used in planning as well as in the or to guide the surgeon. 

我们与一家名为Neurotargeting的公司合作，该公司开发了可作为外科医生的路线图，以了解基于大众分析的关键功能的可能区域。这些地图可用于安排计划以及指导外科医生。

Here was a short video of the type of visual visualization we can provide to the surgeon, in this case, we're looking at an epilepsy patient with probes distributed throughout the brain to identify the regions responsible for convulsive activity. All of this information can be reconstructed in virtual reality. The surgeon can literally deconstruct the brain to understand exactly what's happening, devise the optimal treatment, and then perform it on the real. 

这是我们可以提供给外科医生的视觉可视化类型的简短视频，在这种情况下，我们正在研究一名癫痫患者，探头分布在整个大脑中，以识别引起惊厥活动的区域。所有这些信息都可以在虚拟现实中重建。外科医生可以从理论上解构大脑以准确了解正在发生的事情，设计最佳治疗方法，然后再进行实际治疗。

Now I’ll talk about noninvasive treatments which really represents the most potential for new benefit. By their nature, noninvasive treatments can be readily applied even by the patient at home more dynamically to provide real time treatment of physical or psychological challenges such as schizophrenia. Of course, as these treatments are applied blinded, they pose a particular challenge in determining a protocol that will deliver the desired results. This is, let me show you an example of how virtual brain can be used. 

现在我将讨论无创治疗，它实际上代表了获得新收益的最大潜力。就其性质而言，即使是在家中的患者也可以更动态地应用无创治疗，以提供对诸如精神分裂症等生理疾病或心理疾病的实时治疗。当然，由于这些治疗方法是盲目应用的，因此在确定能够提供所需结果的方案时会带来特殊的挑战。上面的案例让我能够向您展示如何使用虚拟大脑。

In this case study, the authors simulate transcranial electrical stimulation, and once again I’d like to acknowledge the critical work of the collaborators, in this case, leader under the direction of the lead investigator, Dr. G. Venkatasubramanian, at the national Institute for mental health and neuroscience in India. 

在这个案例研究中，作者模拟了经颅电刺 激，我想再次感谢合作者的重要工作，在这个案例中，合作者是首席研究员G. Venkatasubramanian博士，他是印度国家心理健康和神经科学研究所头头。

As I mentioned, the biophysics of electrical brain stimulation is that a predominantly shuns through the skull, stimulating the nerves below with relatively weak field compared to DBS. Since these low fields were non convulsive, the patient can be conscious and feel a little discomfort, offering many different delivery modes, as with all ES (Electrical Stimulation) techniques, both the location and the pulse modality will govern the effectiveness of the treatment. It’s low amplitude two currents don't trigger any action potentials directly, rather they alter the resting potential selectively raising and lowering regions as desired. 

正如我提到的，电刺 激大脑的生物物理学研究可以避免开颅手术，与DBS相比，它以相对弱的电场刺 激下方的神经。由于这些低场是非惊厥性的，因此患者可以保持清醒并感到一些不适，并提供多种不同的实现方式，就像所有ES（电刺 激）技术一样，位置和脉冲方式都将决定治疗的有效性。它的振幅很低，两个电流不会直接触发任何动作电位，而是会根据需要改变静止电位，选择性地升高和降低区域。

In this study, transcranial direct current stimulation is used to treat schizophrenia. In this case, the patient is tested to identify those regions where the action is higher than desired in action where it is lower. The goal of the treatment is then to decrease the resting potential in the areas where the behavior you would like to reduce and raise its potential to increase neural activity in the desirable behaviors. 

在这项研究中，经颅直流电刺 激用于治疗精神分裂症。在这个案例中，对患者进行测试以识别那些要高于动作期望值的动作区域。然后，治疗的目标是减少您想减少行为的部位的静息潜力，并提高其在期望行为中增加神经活动的潜力。

As before, the CT Scans were segmented in this case into six unique sections, each given anisotropic electrical conductivity, which were measured from cadavers. The model was composed of 3,000,000 elements and about 17,000,000 nodes. In the simulation, the current of 2 mA was applied and the exterior was then treated as an insulator so no loss of energy would result. 

和以前一样，在这个案例中，CT扫描被分为六个独特的部分，每个部分都具有各向异性电导率，这些是从尸体上测得的。这个模型由3,000,000个单元和大约17,000,000个节点组成。在仿真中，施加了2毫安的电流，然后将外部视为绝缘体，因此不会造成能量损失。

With these detailed, patient specific models, the exact procedure can be performed on the virtual twin of the patient, with significant benefits of being able to look inside the skull to track the propagation of the electrical signal, and actually looked deep into the brain and see what's happening inside. This gives the clinician the detail they need to be able to tune the location and pulsing sequence to exactly the location to produce the desired effects. 

使用这些详细的，针对特定患者的模型，可以对患者的虚拟双胞胎执行精确的操作，其显著优点是能够查看颅骨内部以跟踪电信号的传播，并可以深入大脑并观察里面发生了什么。这为临床医生提供了所需的详细信息，以便能够将位置和脉冲序列调整到确切的位置以产生所需的疗效。

Easing the procedure described, patients were actually treated and classified as responders and non-responders. In this study, the goal was to understand why the treatment was effective in some, but not in others. And having the ability to look inside the skull, to understand exactly what was happening and compared to experimental measurements was invaluable in understanding the differences. 

通过简化所描述的过程，患者实际上得到了治疗，并被分为有反应者和无反应者。在这项研究中，目标是了解为什么这种疗法对某些人有效，但对另一些人无效。医生能够看清头骨内部，准确了解正在发生的情况并将其与实验测量结果进行比较，对于了解这些差异非常宝贵。

To guide the treatments, in this protocol, the measured excitation potentials, but positive and negative could be mapped back into the clinical data which augmented the scans with virtual surgery information. Having the ability to overlay that the clinical data and simulated data gives insights into the procedure that are invaluable in guiding the treatment and gives real time understanding. 

为了指导治疗，在此方案中，可以将测得的激发电势（阳性和阴性）重新映射回临床数据，从而用虚拟手术信息增强扫描。具有覆盖临床数据和模拟数据的能力，可以洞悉对指导治疗至关重要的程序，并提供实时了解。

Based on the cohort of patients in the studies, the authors were actually able to devise a two-step procedure to optimize the treatment. The first step was to simulate the treatment over the full range of options, creating a map of the response surfaces. The data is then provided to the clinician who is unable to interactively fine tune the treatment based on the insight from the data and any other relevant knowledge and experience. 

根据对患者的研究，作者实际上能够设计出一个两步法来优化治疗方案。第一步是在所有选项范围内模拟处理，创建响应表面图。然后，将数据提供给临床医生，基于对数据的洞察以及其他相关知识和经验进行交互微调治疗。

The result is now a semi-automated digital workflow for creating patient specific treatment protocols, which go from scan data to optimize treatment using the digital twin as the guide. Although the procedure is still under development, over time, the clinical database should provide a fantastic knowledge foundation to dramatically increase the effectiveness of the treatment, and possibly lead to AI models which would then allow real time optimization. 

现在的结果是一个半自动化的数字工作流程，用于创建针对特定患者的治疗方案，该方案从扫描数据开始，以数字双胞胎为指导来优化治疗方案。尽管该程序仍在开发中，但随着时间的流逝，临床数据库会提供丰富的知识基础，以显着提高治疗的有效性，并可能引导AI模型，从而实现实时优化。

And finally, now I described the use of the virtual brain model for the treatment of neuro degenerative diseases. For decades, scientists have speculated that the key to understanding age related neuro degenerative disorders may be found in the unusual biology of the prion diseases, recently this hypothesis has gained experimental momentum. 

最后，我来讲一讲虚拟大脑模型在神经退行性疾病治疗中的使用。几十年来，科学家一直推测、了解与年龄有关的神经退行性疾病的关键可能是在朊毒体疾病的异常生物学中发现的，最近这种假说已经获得了实验动力。

Where it's been observed that specific proteins have been found to miss fold and aggregate into seeds that structurally corrupt similar proteins, causing them to aggregate and form assemblies such as large masses of amyloid. These proteinaceous seeds can then serve as self-propagating agents for the progression of disease. The outcome is the functional compromise in the nervous system because the aggregated proteins become toxic or lose their normal function. In this case study, the authors will investigate these mechanisms. 

有人发现，发现特定的蛋白质会发生错误折叠并聚集到种子中，这些种子会在结构上破坏相似的蛋白质，从而导致它们聚集并形成装配，比如大量淀粉样蛋白。这些蛋白质种子接着可以用作疾病发展的自我繁殖剂。结果导致神经系统的功能受损，因为聚集的蛋白质变得有毒或失去其正常功能。在本案例研究中，作者将研究这些机制。

As I mentioned, the authors explore the hypothesis that these disease progressions are governed by the complex reactions that lead to the propagation of toxic proteins, which then concentrate and create lesions in turn causing cell death and tissue atrophy. There are several possible propagation mechanisms that can be investigated using models which compared to longitudinal clinical data to help understand what's happening in a given patient. 

正如我提到的，作者探索了以下假设：这些疾病的发展受复杂反应的控制，这些反应导致有毒蛋白质的传播，然后有毒蛋白质聚集并形成损伤，进而引起细胞死亡和组织萎缩。与纵向临床数据相比，可以使用模型研究几种可能的传播机制，以帮助了解特定患者的病情。

Of course, each patient will experience dementia uniquely to their own dis-regulation of protein synthesis, but the underlying mechanism of disease progression would be assumed to be similar and the patient will experience a combination of these physical, chemical, and biological factors. 

当然，每位患者都会因自身蛋白质合成失调而遭遇独特的痴呆症，但是疾病发展的潜在机制被认为是相似的，并且患者会经历这些物理、化学和生物学因素的综合作用。

Once again, the brain is reconstructed using the previously described protocols to understand each disease progression, the authors compute the biomarker abnormality and create a temporal map of the toxic protein which is based on clinical observations. Then, using a propagation model, the time evolution of the path of the proteins can be predicted and analyzed. Finally, a tissue atrophy model with different atrophy rates in the grey and white matter area were used to create atrophy maps. For computational efficiency, tissue shrinking is computed in a post processing step based on the values of concentration at different time points.

再一次，使用先前描述的方案重建大脑以了解每种疾病的进展，作者计算了生物标志物异常并基于临床观察结果创建了有毒蛋白质的时间图。然后，使用传播模型，可以预测和分析蛋白质时间演化的路径。最后，使用在灰质和白质区域具有不同萎缩率的组织萎缩模型来创建萎缩图。为了提高计算效率，根据不同时间点的浓度值在后处理步骤中计算组织收缩。

Here's an example of an Alzheimer’s patient. On the left we see activation maps over time, from zero to 15 years following the progression of Tau inclusions. In the center, we see MRI images taken from a patient compared to the predicted time sequence of toxic proteins in the center. And at the center bottom we see the result in brain atrophy predicted from the toxic protein progressions. 

这是阿尔茨海默氏症患者的示例。在左侧，我们可以看到，随着时间的推移，Tau夹杂物的发展，从零到15年的活化图。在中间，我们看到从病人那里获取的MRI图像与中心有毒蛋白质的预测时间序列相比。在中间的底部，我们看到了根据毒性蛋白发展预测的脑萎缩的结果。

Using clinical data, the authors were able to develop a simple model of aggregated trends, neural damage to test the possible interactions between Tau proteins, and amyloid beta. And coupled behavior between these toxic proteins clearance and protopathic propagation. 

利用临床数据，作者能够开发一个简单的汇总趋势、神经损伤模型，以测试Tau蛋白和淀粉样蛋白之间可能的相互作用，以及这些有毒蛋白质清除率和原发病性传播之间的耦合行为。

This is a summary slide which shows 2D animation sequences of four different damage maps. Their analysis suggests that amyloid, beta and Tau proteins work together to enhance nucleation and propagation of different diseases, which sheds new light on the importance of protein clearance and protein interaction mechanisms and prion-like models of inherited degenerative diseases. 

这是一张总结幻灯片，显示了四个不同损伤图的2D动画序列。他们的分析表明，淀粉样蛋白、β蛋白和Tau蛋白可以协同作用，以增强不同疾病的成核和传播，这为蛋白清除和蛋白相互作用机制以及遗传性疾病的类似朊毒体模型提供了非常重要的新思路。

Of course we understand the importance of three dimensions in understanding the actual effect on the human body. So here we see 3D progression maps which could be further interrogated to reveal more insights into the psychological impact of these disease progression. On the left we see how inclusions in Alzheimer’s disease on the right Alphas in nuclear inclusions in Parkinson disease. Clearly we see very different progressions, this can provide insights into understanding treatment protocols and better behavior. 

当然，我们了解三维在理解对人体的实际影响方面的重要性。因此，在这里我们看到了3D进程图，可以对其进行进一步探索以揭示出对这些疾病进程的生理和心理影响的更多洞察。在左侧，我们看到帕金森氏病的核内包裹物，在右侧的阿尔茨海默氏病中的包裹物。显然，我们看到了截然不同的发展，这可以为理解治疗方案和更好的行动方案提供洞察力。

As I mentioned, the authors were able to couple the progression maps with physical atrophy models that mimic clinically observable changes in the brain morphology. This animation we see the displacements of the brain atrophy, which are exaggerated to aid visual interpretation, but provide very meaningful insights into understanding what's happening at the physical level and can be compared directly to clinical data. 

正如我提到的，作者能够将发展图与模仿临床形态上可观察到的大脑形态变化的物理萎缩模型相结合。这个动画我们看到了脑萎缩的位移，它被夸大了以帮助进行视觉解释，但是提供了非常有意义的见解，以了解物理水平上发生的事情，并且可以直接与临床数据进行比较。

In the future, the authors hoped to include a connectome-based dementia model, which could significantly add to the fidelity of the patient representation and interpretation of what actually may be happening to the patient itself. 

在将来，作者希望包括一个基于神经连接体的老年痴呆症模型，该模型可以显著增加患者表达的保真度并解释患者自身实际可能发生的情况。

Once again, I need to recognize the authors of this work and recommend that you contact them or look up their publications if you're interested in further information on their work. We also show here a nice 3D visualization, which superimposed many of the factors that I’ve discussed demonstrating the ability for three dimensional representations to capture very complex human behavior. 

再一次，我需要认识这项工作的作者，如果您对他们的工作的进一步信息感兴趣，建议您与他们联系或查阅他们的出版物。我们还在这里展示了一个不错的3D可视化效果，它叠加了我已经讨论过的许多因素，这些因素证明了三维表示法能够捕获非常复杂的人类行为。

Taking a look ahead, we believe we now have assembled many of the techniques in place to be able to simulate complex patient specific treatment protocols. In addition to those I’ve shown, were exploring drug delivery mechanisms, such as those delivered directly through the cerebral spinal fluid to allow for regional or concentration specificity. 

展望未来，我们相信我们现在已经组装了许多技术，能够模拟复杂的特定患者治疗方案。除了我已经展示过的那些药物外，还在探索药物的输送机制，例如那些直接通过脑脊髓液输送的药物，以实现区域或浓度特异性。

Beginning with what we've learned about simulating micro vascular systems, the complex interactions between fluids and soft tissues such as valves, as well as needle penetration skin permeability etc. Our multi-scale models can help us go from cellular interactions to an entire patient, which can be built up from scan data, or ultimately approximated from libraries or Atlases. We think this is the horizon of a truly patient centric medicine and will transform the patient experience forever. 

从我们所学到的关于模拟微血管系统的知识开始，流体和软组织（例如瓣膜）之间的复杂相互作用以及针头穿透皮肤的渗透性等。我们的多尺度模型可以帮助我们从细胞相互作用到整个患者，可以从扫描数据中构建，也可以最终从数据库或图谱中近似得出。我们认为这是真正以患者为中心的医学的视野，它将永远改变患者的就医体验。

In summary, I’ve tried to give you a flavour of how we've spent the last five years or so creating digital continuity between real patients and virtual patients. We know from experience that the marriage of the real world and virtual worlds really is the key to unlocking the imagination of medical and biomedical innovators. 

总而言之，我试图向您介绍过去五年来我们在真实患者和虚拟患者之间建立数字连续性的方式。我们从体验中获知，真实世界和虚拟世界的结合确实是释放医学和生物医学创新者想象力的关键。

Although there's still a long way to go, I hope I’ve convinced you that virtual human twin is really on the horizon, and it can be the transformational element that connects our disciplines, translates fundamental understanding into clinical care. We've made good progress with the living heart and more recently, with the brain, and we hope to continue to map ultimately to the entire human body. 

尽管还有很长的路要走，但我希望我已经说服了您，虚拟人体双胞胎的时代的确即将到来，它可能是连接我们各个学科，将基本知识转化为临床护理的革命性要素。我们在“活体心脏”方面以及在最近的“活体大脑”方面都取得了良好的进展，我们希望继续最终映射到整个人体。

And of course, the digital twin can always be accessed on the Cloud so they'll always with you or your doctor, or maybe one day with your coach to guide safer sports. 

当然，始终可以在云端访问数字双胞胎，因此他们将始终与您或您的医生在一起，或者也许有一天与您的教练一起指导更安全的运动。