Nanomedicine, Volume I: Basic Capabilities

© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999


 

8.4.2 Barographic Navigation

The internal pressure field of the human body (already briefly summarized in Sections 4.9.1, 6.3.3, and 8.2) is as complex as the temperature field. (Section 9.4.1 discusses the rheology of the circulation.)361 In general, fluid pressures range from 60-150 mmHg in the heart, arteries and arterioles; ~30 mmHg in the capillaries and 5-20 mmHg in the veins; 4-30 mmHg in the pulmonary artery; 9-13 mmHg in the cerebrospinal and synovial fluids; ~1.4 mmHg in the interstitial fluid between cells; and ~0.9 mmHg mean pressure in the lymphatics, with arterial pulsations contributing 1.5-2.2 mmHg oscillations with a maximum of ~5 mmHg in the lymphatics. (Systolic pressure may reach a maximum of ~230 mmHg during the heaviest exercise.)

As in thermographics, simple barographic demarcation provides a ready means for directing medical nanorobots to a desired treatment location within the body. Simply pressing down on the surface of the skin creates an anomalous region of elevated tissue pressure; tapping, slapping, or palpitating the body's surface is also detectable by in vivo nanorobots (e.g., Section 7.4.2.1). Acoustically active catheters inserted transdermally can place a sonic beacon signal near almost any target location. Highly focused but relatively low power (to reduce reflection echo detection) ultrasonic columnar or planar beams of, say, three different frequencies can be directed into the body on various trajectories and from various sources. The tiny spot where all three frequencies are audible at precisely equal intensity marks the target, providing <~1 mm3 localization accuracy at frequencies >~1.5 MHz. Focused ultrasound surgery (FUS) and high-intensity focused ultrasound (HIFU) may use ~2-second bursts of 1.7-MHz, 150-mm-deep focused beams at 5 x 107 watts/m2 to occlude blood flow or destroy tumors by creating a spot of intense heat so small that there is a boundary of only ~6 cells between destroyed tissues and completely unharmed tissues, a ~100 micron spatial resolution.1647

As in the case of temperature fields, low-resolution and high-resolution barographic maps can be compiled and stored by barographicytes, then used to diagnose a wide variety of medically relevant states in organs and throughout the body including tumors, edemas, excess cranial pressure, general hypertension or hypotension, swollen lymph glands, muscle spasms and the like. Such maps are also useful in macrosensing, as for instance to help determine if the patient is sitting,3330 standing, prone, inverted, falling, or floating (Section 4.9.2). Blood pressure increases in patients who are exercising, eating a meal, or emotive (e.g., angry), and decreases in patients who are relaxing or sleeping. The typical daily readings in a hypertensive 35-year-old male might be 150-220 mmHg systolic and 90-140 mmHg diastolic.

However, the amplitude and timing of pressure waves in the blood vessels permit somewhat clearer positional inferences than is possible with thermographics, in part because the heart is such a strong, reliable, and stably-positioned acoustic pulse generator.* Functional hemobaric mapping thus may provide useful positional information regarding vascular range estimates.


* In 1998, heart sounds originating from multiple sites within the four chambers of the heart, its valves and the great vessels remained difficult to analyze. Despite the close coincidence of valve closure and high frequency components in the first heart sound (echocardiographic corroboration), the exact mechanism of sound production was poorly understood.1302 Phonocardiograms (PCGs) are distorted during transmission through the chest wall; cardiac auscultation, traditionally used to detect a wide variety of normal and pathological heart conditions, was still more art than science.3339-3342


For example, Figure 8.29 shows the change in shape and amplitude of the pressure wave with increasing distance downstream from the aortic valve (where the left ventricle of the heart initially discharges into the descending aorta). There are three features of interest. First, each successive profile shifts to the right, suggesting wave propagation. Second, the sharp dicrotic notch in the pressure record (marking the closure of the aortic valve) is gradually lost in successive profiles, a clear navigational marker of aortic range.

Third, there is a steepening and increasing of amplitude in successive profiles, indicating a rise in peak systolic pressure with distance from the heart. This counterintuitive increase is a dynamic phenomenon of an elastic branching system with tapered tubes -- with steady flow in a rigid tube of similar diameter and taper, pressure always decreases in the direction of flow unless there is deceleration.361 Note that the mean pressure averaged over a full heartbeat still decreases with increasing distance from the aortic valve -- by ~4 mmHg over the full length of the aorta -- while the amplitude of the systolic/diastolic pressure oscillation nearly doubles.361 Measurements in dogs show that this peak pressure pulse amplification process continues until about the third generation of arterial branchings, after which both the oscillation and the mean pressure decrease gradually downstream along the arterial tree.361 These pulse profiles can probably be resolved with sufficient accuracy to allow a medical nanorobot equipped with appropriate pressure sensors to fix its position along all the main trunks of the arterial tree to within at least ~1 cm, and perhaps better.

Pressure and velocity waveforms change in different ways along the branches of the tree,924 in part due to reflection at bifurcations, which may allow bloodborne nanorobots to distinguish the organ in which they currently reside. For instance, the waveforms found in the renal and iliac arteries are quite distinct.924

Approximate position in the venous tree is readily inferred as well. For example, mean pressure in the venules is ~18 mmHg with fluctuations of amplitude ~3 mmHg; by the time bloodborne nanorobots reach the upper vena cava, near the right atrium of the heart, the mean pressure has fallen to ~2.2 mmHg with pressure fluctuations of amplitude ~5 mmHg.361

Microvascular position can also be estimated from various local pressure measurements.929 For instance, Figure 8.30 shows a typical pressure-velocity distribution in arteriovenous microvessels 8-60 microns in diameter in the cat mesentery. Knowledge of mean local pressure and flow velocity identifies vessel diameter to within 5 microns. Additionally, these pressure distribution profiles differ markedly from one tissue to another (Fig. 8.31). Comparison of the measured profile against a library of such profiles will at least narrow the possibilities, if not produce a unique tissue identification.

Local hematocrit (the volume fraction of red cells in whole blood, or Hct) varies as a function of microvessel diameter (Fig. 8.32). Simple omnidirectional echolocation (Section 4.8.2) measures the average distance to the nearest red blood cell over many samples -- e.g., the mean center-to-center distance between red cells is ~9.8 microns at Hct 10%, ~6.8 microns at Hct 30%. An acoustic test pulse travels ~1.5 microns in 1 nanosec, hence Hct 10% and Hct 12.7% are distinguishable using one round-trip measurement, allowing a medical nanorobot to estimate the local microvessel diameter to within approximately 10 microns. Given the scatter in the data, multiple measurements should improve the accuracy of the estimate.

Maps of mechanical properties such as strain fields in tissues can also provide useful navigational information but will be more difficult for individual nanorobots to employ directly. Magnetic resonance elastography (MRE) has already been used experimentally to map the shear modulus field of a porcine kidney using shear wave excitation at 200-400 Hz.928 Shear waves with displacements under 100 nm were readily observed, and it is believed the technique may be useful in mapping other viscoelastic parameters such as attenuation and dispersion, allowing more detailed tissue characterization. Elastographic parameters are highly variable in time as well as space. For example, the viscoelasticity of cervical mucus secretions swings widely over the course of the menstrual cycle, with a major feature occurring at mid-period near ovulation time,922 mirroring the temperature changes (Section 8.4.1.1)

 


Last updated on 20 February 2003