दुर्भाग्य से, यह वेबसाइट हिंदी में नहीं बल्कि जर्मन या अंग्रेजी में उपलब्ध है

It is a truism that the normal function of any organ depends on a sufficient supply with blood. However, the proper evaluation of blood supply is still in its infancy. In daily medical routine the measurement of blood supply only involves arterial influx [1]. The venous side of the circulation is less well investigated. However, since blood needs to circulate from the heart to the peripheral organs and back again, the function of the veins — returning blood to the heart — is equally important to the arterial influx.

he damage to an organ resulting from a disturbed blood supply can be evaluated relatively easily by testing its function. This can be done through laboratory tests, such as measuring blood levels of enzymes and metabolic products, and functional tests, such as performance tests, EEGs, ECGs and scintigraphy.

From a patient’s perspective, impaired function manifests as a symptom.

The normal organs’ blood supply while resting is given in the table below

( from GUYTON AND HALL TEXTBOOK OF MEDICAL PHYSIOLOGY, 14. Ed. 2021, Table 17-1 p 206: in https://cuvas.edu.pk/cuvas_libraries/ebooks/guyton-and-hall-textbook-of-medical-physiology-14th-edition_043155.pdf )    [2]

Arterial cerebral perfusion runs via the internal carotid arteries (72–80%), the vertebral arteries (20–28%), and the spinal arteries (with negligible flow volumes, which are negligible for brain supply).

Venous cerebral perfusion is realised by the internal jugular veins, the vertebral veins, and the external and internal spinal veins (epidural and perispinal), which have the following flow volumes:

With only about 2% of the body weight the brain receives 15% of the cardiac output.

Many cerebral and neurological symptoms are related to increased intracranial pressure or disturbed perfusion of certain parts of the brain. The rise of intracranial pressure is a consequence of increasing volume of intracranial structures while the intracranial space remains constant. The intracranial space of an adult is roughly 1500 mL (female) to 1600 mL (male) while the brain volumes are 1300/1400 mL respectively. The fact that the volume difference is only 200 ml, compared to blood flow volumes of 700 ml/min on both the arterial and venous sides, highlights the importance of fine-tuning arterial and venous brain perfusion to prevent a rapid increase in intracranial pressure. If a venous obstruction occurs, the only possible shift in volume is the displacement of cerebrospinal fluid. Its intracranial volume is approximately 180 ml in both sexes, and it is not easily shifted due to its partial location in the intracranial ventricles. The remaining peripheral CSF can be expelled from the skull into spinal reservoirs, but this creates little additional space for trapped venous blood.

The consequences of increased intracranial pressure are wide ranging from dizziness and headaches to vomiting, visual disturbances, dysfunction of the cranial nerves and autonomic disturbances [3] and in the emergency setting even brain herniation, ischemia and death [4].

Chronically increased intracranial pressure is less easily suspected when the main symptoms are fluctuating and less severe, such as various kinds of headaches, creeping vision loss, palsy of the sixth cranial nerve causing double vision, pulsatile tinnitus and dizziness, which nevertheless interfere with normal daily activities.

Idiopathic chronic intracranial hypertension is a disease that mainly affects women and is of unknown origin. Chronic fatigue syndrome may be an early stage of increased intracranial pressure [5].

Precise measurement of intracranial pressure requires invasive techniques, which are not feasible in an outpatient setting. However, cerebral MRI and CT scans can provide clues when the peripheral CSF is reduced and the ventricles are narrower or wider than normal.

I developed a novel, non-invasive functional and quantitative method which is suitable for outpatient evaluation and does not require injection of contrast media-the global arterial and venous brain perfusion measurement with the 4D- PixelFlux technique.

This method was introduced on the basis that constant intracranial pressure requires balanced arterial inflow and venous outflow to and from the skull. If the venous outflow is restricted, or if additional venous volume enters the skull via the epidural and perispinal veins, then the intracranial pressure will become elevated. The intracranial pressure may increase further if this imbalance is unstable.

Colour Doppler ultrasound is the preferred method to evaluate the cranial blood supply since it is harmless, widely available, requires no preparation and is non-invasive. So far however only approximated arterial flow volumes could be calculated with a simple two-dimensional technique while reliable venous flow measurements were out of reach.

For arteries a good approximation was achieved since the flow volume can be estimated by multiplying the mean flow velocity which is measured during the colour Doppler examination of the vertebral and carotid arteries with the transsectional area of the vessel. This area is calculated by simply measuring the largest diameter of the vessel and calculating the area by  the circle-area formula. this is not quite exact but a workable approximation.

However, this method is completely misleading in veins. This is due to the strong variability of the cross-sectional area of the vein, which rarely resembles a circle, and the uneven distribution of flow velocities inside the large cervical veins. Flow velocities and area also change significantly due to backpressure from the heart, the effect of respiration, and the neighbouring arteries and muscles. In addition, veins are heavily affected by changes in head position.

To overcome these limitations, we developed the 4D-PixelFlux technique. This enables precise, pixel-wise measurement of flow velocities and the transsectional area of all cervical blood vessels including veins for the first time, taking into account their ever-changing shape and course during head movements.

Moreover, this technique for the first time can calculate potential discrepancies of arterial influx via the carotid and vertebral arteries and the venous outflow via the internal jugular veins and vertebral veins.

This is of the utmost importance in cases of vascular compression syndrome in the abdomen, pelvis, thorax and neck. The spinal canal is an alternative route for many of these compression syndromes, as the vessels within it are protected from local compression. Blood that enters the spinal canal rises within the spine and can enter the skull via the greater foramen at the base of the skull, which contains the medulla oblongata.

With the simultaneous determination of the true flow volumes within both carotid arteries, both vertebral arteries, both internal jugular veins on both vertebral veins we can measure the influx from the spinal canal into the skull contributing to the increased intracranial pressure. There is no relevant arterial influx via the greater foramen. The volume flow difference of the main cervical arteries and veins is thus the additional spinal flow volume.

If such a situation exists the body usually responds with increased outflow via the internal jugular veins. There is little additional transport capacity of the vertebral veins since they are surrounded by the bony foramina in the of the lateral processi of the cervical vertebrae.

If an influx into the spinal canal exists due to venous compression syndromes, the cervical veins are often compressed simultaneously, since increased lumbar lordosis is the cause of all compression syndromes, and this is often accompanied by increased cervical lordosis. This results in compression of the internal jugular vein between the carotid arteries, the omohyoid muscle, and the sternocleidomastoid muscle in the middle of the neck. In such a situation the adaptation to additional spinal influx may cause increased intracranial pressure which can be demonstrated by the flow acceleration at the compression site of the internal jugular vein.

Simultaneously evaluating this pressure gradient and flow volume discrepancy is key to understanding many of the patients’ cerebral symptoms resulting from increased intracranial pressure, which conventional techniques fail to detect.

Case presentation

I present the case of an 18-year-old female patient who has suffered from left-sided migraines, extreme chronic fatigue, exhaustion, weakness in all four limbs, brain fog, hot flushes, dizziness and abdominal pain for two years. Other notable symptoms included severe menstrual pain, a 5 kg weight loss, nausea and an inability to stand for more than five minutes.

She had clear clinical signs of a hypermobility disorder (hypermobile Ehlers-Danlos syndrome). The functional sonographic diagnostics revealed severe pelvic congestion syndrome as a consequence of the combination of may Thurner syndrome and left renal vein compression with a broad collateralisation via a tall vein a tronc réno-rachidièn towards the spinal canal. In addition a beginning median arcuate ligament syndrome and a severe right-sided orthostatic nephroptosis was found. During the examination and orthostatic syncope occurred.

Compression of the left internal jugular vein between the sternocleidomastoid muscle and the common carotid artery produced only slight localised flow acceleration, from 24 to 47 cm/s. In contrast, the wider right internal jugular vein exhibited a much stronger flow acceleration despite a less severe compression at the same cervical level, from 53 to 131 cm/s.

Such a discrepancy cannot be explained using conventional colour Doppler techniques. The usual finding is that the faster the flow acceleration, the greater the narrowing of the blood vessel. In this case, however, the opposite was true.

The resolution of this dilemma and explanation of the left-sided headaches, chronic fatigue, brain fog, dizziness was only found with the global arterial and venous 4D- Pixel Flux volume flow measurements of all brain supplying cervical blood vessels.

A 4D volume flow measurement is carried out with the patient lying on her back without a pillow, with head in a neutral position. The measurements are outlined in the diagram below. A comparison with normal flow volumes, as indicated below the diagram, shows that the internal jugular veins have different transport capacities. The left vein transports less than 50% of the normal mid-range volume, whereas the right vein has compensatory hyperperfusion, balancing out the loss on the left side. This corresponds to the patient’s left-sided migraine.

The arterial flow volume on the left is 330 ml/min, whereas on the right it is 385 ml/min, which is not a relevant difference.

The overall arterial flow volume is therefore 715 ml/min. The venous outflow from the skull is 167 mL/min on the left side and 665 mL/min on the right side since the vertebral vein cannot compensate for the reduced perfusion volume of the internal jugular vein on the left side.

The overall venous drainage volume is 832 mL/min.

This differs from the arterial influx by 117 mL/min, which corresponds to a venous overload from the spinal canal of 16% of cerebral perfusion.

These measurements show that, on the left side, symmetric arterial brain perfusion meets outflow resistance, necessitating a volume shift within the skull from left to right in order to drain venous blood. This corresponds to the pressurisation of the left intracranial hemisphere, which explains the patient’s left-sided migraine. This is due to the tronc réno-rachidièn, which pumps 270–590 ml/min of blood from the compressed left renal vein towards the spinal canal. The varying volumes are due to changes in body posture; the patient was evaluated in both the horizontal and standing positions. While the cervical 4D- PixelFlux flow volume measurements do not show the total flow volume over time of the tronc réno-rachidièn pointing to an exit of parts of the volume on its way up to the skull via the intervertebral foramina, the influx is strong enough to produce the aforementioned symptoms and flow accelerations. It is now clear that the significant acceleration in flow despite the only slight compression of the right internal jugular vein is due to its volume overload, since the left internal jugular vein is unable to provide the necessary transport capacity.

The mean flow volumes of the internal jugular veins in healthy individuals have been determined as follows:

Left internal jugular vein:    mean 258.6  ml/min (SD 133.8 ml/min)

Right internal jugular vein:  mean 460.8 ml/min (SD 193.8 ml/min) [6]

Common carotid arteries 470±120 ml/min [7]

The video above describes the 4D- PixelFlux volumetric flow measurement Illustrated on 3 different vessels of the same patient

Literature

1. Michael Peters, A., The precise physiological definition of tissue perfusion and clearance measured from imaging. European Journal of Nuclear Medicine and Molecular Imaging, 2018. 45(7): p. 1139–1141.
2. Hall, J.E., Hall M.E., GUYTON AND HALL TEXTBOOK OF MEDICAL PHYSIOLOGY, 14. Ed. 2021. 2021: Elsevier.
3. Dunn, L.T., RAISED INTRACRANIAL PRESSURE. Journal of Neurology, Neurosurgery & Psychiatry, 2002. 73(suppl 1): p. i23–i27.
4. Olaru, C., S. Langberg, and N.S. McCoin, A review of the clinical presentation, causes, and diagnostic evaluation of increased intracranial pressure in the emergency department. Western Journal of Emergency Medicine, 2024. 25(6): p. 1003.
5. Higgins, J.N.P. and J.D. Pickard, A paradigm for chronic fatigue syndrome: caught between idiopathic intracranial hypertension and spontaneous intracranial hypotension; caused by cranial venous outflow obstruction. Fatigue, 2021. 9(3): p. 139–147.
6. Feng, W., et al., Quantitative flow measurements in the internal jugular veins of multiple sclerosis patients using magnetic resonance imaging. Reviews on recent clinical trials, 2012. 7(2): p. 117–126.
7. Schöning, M., J. Walter, and P. Scheel, Estimation of cerebral blood flow through color duplex sonography of the carotid and vertebral arteries in healthy adults. Stroke, 1994. 25(1): p. 17–22.